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Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?

  • Review Article
  • Theme: Natural Products as Therapeutic Modulators
  • Published:
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Abstract

Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail.

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REFERENCES

  1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  PubMed  CAS  Google Scholar 

  2. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett. 2008;267:133–64.

    Article  PubMed  CAS  Google Scholar 

  3. Vogel P (1815) J Pharm 50

  4. Daybe FV (1870) Uber Curcumin, den Farbstoff der Curcumawurzzel. 609

  5. Kiuchi F, Goto Y, Sugimoto N, Akao N, Kondo K, Tsuda Y. Nematocidal activity of turmeric: synergistic action of curcuminoids. Chem Pharm Bull (Tokyo). 1993;41:1640–3.

    CAS  Google Scholar 

  6. Aggarwal BB, Sethi G, Baladandayuthapani V, Krishnan S, Shishodia S. Targeting cell signaling pathways for drug discovery: an old lock needs a new key. J Cell Biochem. 2007;102:580–92.

    Article  PubMed  CAS  Google Scholar 

  7. Huang MT, Wang ZY, Georgiadis CA, Laskin JD, Conney AH. Inhibitory effects of curcumin on tumor initiation by benzo[a]pyrene and 7, 12-dimethylbenz[a]anthracene. Carcinogenesis. 1992;13:2183–6.

    Article  PubMed  CAS  Google Scholar 

  8. Conney AH, Lysz T, Ferraro T, et al. Inhibitory effect of curcumin and some related dietary compounds on tumor promotion and arachidonic acid metabolism in mouse skin. Adv Enzyme Regul. 1991;31:385–96.

    Article  PubMed  CAS  Google Scholar 

  9. Huang MT, Smart RC, Wong CQ, Conney AH. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1988;48:5941–6.

    PubMed  CAS  Google Scholar 

  10. Bilmen JG, Khan SZ, Javed MH, Michelangeli F. Inhibition of the SERCA Ca2+ pumps by curcumin. Curcumin putatively stabilizes the interaction between the nucleotide-binding and phosphorylation domains in the absence of ATP. Eur J Biochem. 2001;268:6318–27.

    Article  PubMed  CAS  Google Scholar 

  11. Barry J, Fritz M, Brender JR, Smith PE, Lee DK, Ramamoorthy A. Determining the effects of lipophilic drugs on membrane structure by solid-state NMR spectroscopy: the case of the antioxidant curcumin. J Am Chem Soc. 2009;131:4490–8.

    Article  PubMed  CAS  Google Scholar 

  12. Epand RF, Martinou JC, Fornallaz-Mulhauser M, Hughes DW, Epand RM. The apoptotic protein tBid promotes leakage by altering membrane curvature. J Biol Chem. 2002;277:32632–9.

    Article  PubMed  CAS  Google Scholar 

  13. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–57.

    PubMed  CAS  Google Scholar 

  14. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306.

    Article  PubMed  CAS  Google Scholar 

  15. Nicholson DW, Thornberry NA. Caspases: killer proteases. Trends Biochem Sci. 1997;22:299–306.

    Article  PubMed  CAS  Google Scholar 

  16. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995;267:1456–62.

    Article  PubMed  CAS  Google Scholar 

  17. Fadeel B, Orrenius S, Zhivotovsky B. Apoptosis in human disease: a new skin for the old ceremony? Biochem Biophys Res Commun. 1999;266:699–717.

    Article  PubMed  CAS  Google Scholar 

  18. Wyllie AH, Beattie GJ, Hargreaves AD. Chromatin changes in apoptosis. Histochem J. 1981;13:681–92.

    Article  PubMed  CAS  Google Scholar 

  19. Clarke PG. Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl). 1990;181:195–213.

    CAS  Google Scholar 

  20. Stromhaug PE, Klionsky DJ. Approaching the molecular mechanism of autophagy. Traffic. 2001;2:524–31.

    Article  PubMed  CAS  Google Scholar 

  21. Overholtzer M, Mailleux AA, Mouneimne G, et al. A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion. Cell. 2007;131:966–79.

    Article  PubMed  CAS  Google Scholar 

  22. Fadok VA, Voelker DR, Campbell PA, Cohen JJ, Bratton DL, Henson PM. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J Immunol. 1992;148:2207–16.

    PubMed  CAS  Google Scholar 

  23. Sperandio S, Poksay K, de Belle I, et al. Paraptosis: mediation by MAP kinases and inhibition by AIP-1/Alix. Cell Death Differ. 2004;11:1066–75.

    Article  PubMed  CAS  Google Scholar 

  24. Wang Y, Li X, Wang L, et al. An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression. J Cell Sci. 2004;117:1525–32.

    Article  PubMed  CAS  Google Scholar 

  25. Frisch SM, Francis H. Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol. 1994;124:619–26.

    Article  PubMed  CAS  Google Scholar 

  26. Meredith JE Jr, Fazeli B, Schwartz MA. The extracellular matrix as a cell survival factor. Mol Biol Cell. 1993;4:953–61.

    PubMed  CAS  Google Scholar 

  27. Mailleux AA, Overholtzer M, Schmelzle T, Bouillet P, Strasser A, Brugge JS. BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. Dev Cell. 2007;12:221–34.

    Article  PubMed  CAS  Google Scholar 

  28. Thayyullathil F, Chathoth S, Hago A, Patel M, Galadari S. Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. Free Radic Biol Med. 2008;45:1403–12.

    Article  PubMed  CAS  Google Scholar 

  29. Lin SS, Huang HP, Yang JS et al. (2008) DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway. Cancer Lett

  30. Park K, Lee JH. Photosensitizer effect of curcumin on UVB-irradiated HaCaT cells through activation of caspase pathways. Oncol Rep. 2007;17:537–40.

    PubMed  CAS  Google Scholar 

  31. Su CC, Lin JG, Li TM, et al. Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3. Anticancer Res. 2006;26:4379–89.

    PubMed  CAS  Google Scholar 

  32. Tan TW, Tsai HR, Lu HF, et al. Curcumin-induced cell cycle arrest and apoptosis in human acute promyelocytic leukemia HL-60 cells via MMP changes and caspase-3 activation. Anticancer Res. 2006;26:4361–71.

    PubMed  CAS  Google Scholar 

  33. Sikora E, Bielak-Zmijewska A, Magalska A, et al. Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells. Mol Cancer Ther. 2006;5:927–34.

    Article  PubMed  CAS  Google Scholar 

  34. Kang SK, Cha SH, Jeon HG. Curcumin-induced histone hypoacetylation enhances caspase-3-dependent glioma cell death and neurogenesis of neural progenitor cells. Stem Cells Dev. 2006;15:165–74.

    Article  PubMed  CAS  Google Scholar 

  35. Gao X, Deeb D, Jiang H, Liu YB, Dulchavsky SA, Gautam SC. Curcumin differentially sensitizes malignant glioma cells to TRAIL/Apo2L-mediated apoptosis through activation of procaspases and release of cytochrome c from mitochondria. J Exp Ther Oncol. 2005;5:39–48.

    PubMed  Google Scholar 

  36. Qiu S, Tan SS, Zhang JA, et al. Apoptosis induced by curcumin and its effect on c-myc and caspase-3 expressions in human melanoma A375 cell line. Di Yi Jun Yi Da Xue Xue Bao. 2005;25:1517–21.

    PubMed  CAS  Google Scholar 

  37. Wu Q, Chen Y, Li XG. Effect of curcumin on caspase 8- and caspase 9-induced apoptosis of lymphoma Raji cell. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005;13:624–7.

    PubMed  CAS  Google Scholar 

  38. Belakavadi M, Salimath BP. Mechanism of inhibition of ascites tumor growth in mice by curcumin is mediated by NF-kB and caspase activated DNase. Mol Cell Biochem. 2005;273:57–67.

    Article  PubMed  CAS  Google Scholar 

  39. Rashmi R, Santhosh Kumar TR, Karunagaran D. Human colon cancer cells differ in their sensitivity to curcumin-induced apoptosis and heat shock protects them by inhibiting the release of apoptosis-inducing factor and caspases. FEBS Lett. 2003;538:19–24.

    Article  PubMed  CAS  Google Scholar 

  40. Anto RJ, Maliekal TT, Karunagaran D. L-929 cells harboring ectopically expressed RelA resist curcumin-induced apoptosis. J Biol Chem. 2000;275:15601–4.

    Article  PubMed  CAS  Google Scholar 

  41. Bush JA, Cheung KJ Jr, Li G. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res. 2001;271:305–14.

    Article  PubMed  CAS  Google Scholar 

  42. Piwocka K, Jaruga E, Skierski J, Gradzka I, Sikora E. Effect of glutathione depletion on caspase-3 independent apoptosis pathway induced by curcumin in Jurkat cells. Free Radic Biol Med. 2001;31:670–8.

    Article  PubMed  CAS  Google Scholar 

  43. Pan MH, Chang WL, Lin-Shiau SY, Ho CT, Lin JK. Induction of apoptosis by garcinol and curcumin through cytochrome c release and activation of caspases in human leukemia HL-60 cells. J Agric Food Chem. 2001;49:1464–74.

    Article  PubMed  CAS  Google Scholar 

  44. Piwocka K, Bielak-Mijewska A, Sikora E. Curcumin induces caspase-3-independent apoptosis in human multidrug-resistant cells. Ann N Y Acad Sci. 2002;973:250–4.

    Article  PubMed  CAS  Google Scholar 

  45. Piwocka K, Zablocki K, Wieckowski MR, et al. A novel apoptosis-like pathway, independent of mitochondria and caspases, induced by curcumin in human lymphoblastoid T (Jurkat) cells. Exp Cell Res. 1999;249:299–307.

    Article  PubMed  CAS  Google Scholar 

  46. Ghosh AK, Kay NE, Secreto CR, Shanafelt TD. Curcumin inhibits prosurvival pathways in chronic lymphocytic leukemia B cells and may overcome their stromal protection in combination with EGCG. Clin Cancer Res. 2009;15:1250–8.

    Article  PubMed  CAS  Google Scholar 

  47. Hussain AR, Ahmed M, Al-Jomah NA, et al. Curcumin suppresses constitutive activation of nuclear factor-kappa B and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines. Mol Cancer Ther. 2008;7:3318–29.

    Article  PubMed  CAS  Google Scholar 

  48. Jung EM, Park JW, Choi KS, Lee HI, Lee KS, Kwon TK. Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation. Carcinogenesis. 2006;27:2008–17.

    Article  PubMed  CAS  Google Scholar 

  49. Jung EM, Lim JH, Lee TJ, Park JW, Choi KS, Kwon TK. Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis. 2005;26:1905–13.

    Article  PubMed  CAS  Google Scholar 

  50. Wu Y, Chen Y, Xu J, Lu L. Anticancer activities of curcumin on human Burkitt's lymphoma. Zhonghua Zhong Liu Za Zhi. 2002;24:348–52.

    PubMed  Google Scholar 

  51. Srivastava RK, Chen Q, Siddiqui I, Sarva K, Shankar S. Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21(/WAF1/CIP1). Cell Cycle. 2007;6:2953–61.

    PubMed  CAS  Google Scholar 

  52. Liu E, Wu J, Cao W, et al. Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma. J Neurooncol. 2007;85:263–70.

    Article  PubMed  CAS  Google Scholar 

  53. Shankar S, Srivastava RK. Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol. 2007;30:905–18.

    PubMed  CAS  Google Scholar 

  54. Song G, Mao YB, Cai QF, Yao LM, Ouyang GL, Bao SD. Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression. Braz J Med Biol Res. 2005;38:1791–8.

    Article  PubMed  CAS  Google Scholar 

  55. Tsvetkov P, Asher G, Reiss V, Shaul Y, Sachs L, Lotem J. Inhibition of NAD(P)H:quinone oxidoreductase 1 activity and induction of p53 degradation by the natural phenolic compound curcumin. Proc Natl Acad Sci U S A. 2005;102:5535–40.

    Article  PubMed  CAS  Google Scholar 

  56. Choudhuri T, Pal S, Das T, Sa G. Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem. 2005;280:20059–68.

    Article  PubMed  CAS  Google Scholar 

  57. Liontas A, Yeger H. Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer Res. 2004;24:987–98.

    PubMed  CAS  Google Scholar 

  58. Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett. 2002;512:334–40.

    Article  PubMed  CAS  Google Scholar 

  59. Han SS, Chung ST, Robertson DA, Ranjan D, Bondada S. Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53. Clin Immunol. 1999;93:152–61.

    Article  PubMed  CAS  Google Scholar 

  60. Jee SH, Shen SC, Tseng CR, Chiu HC, Kuo ML. Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Invest Dermatol. 1998;111:656–61.

    Article  PubMed  CAS  Google Scholar 

  61. Singh M, Singh N (2009) Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells. Mol Cell Biochem

  62. Shankar S, Chen Q, Sarva K, Siddiqui I, Srivastava RK. Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis. J Mol Signal. 2007;2:10.

    Article  PubMed  CAS  Google Scholar 

  63. Rashmi R, Kumar S, Karunagaran D. Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispensable with ectopic expression of Smac or downregulation of Bcl-XL. Carcinogenesis. 2005;26:713–23.

    Article  PubMed  CAS  Google Scholar 

  64. Rashmi R, Kumar S, Karunagaran D. Ectopic expression of Bcl-XL or Ku70 protects human colon cancer cells (SW480) against curcumin-induced apoptosis while their down-regulation potentiates it. Carcinogenesis. 2004;25:1867–77.

    Article  PubMed  CAS  Google Scholar 

  65. Cheah YH, Nordin FJ, Sarip R, et al. Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231. Cancer Cell Int. 2009;9:1.

    Article  PubMed  CAS  Google Scholar 

  66. Priya S, Sudhakaran PR. Cell survival, activation and apoptosis of hepatic stellate cells: modulation by extracellular matrix proteins. Hepatol Res. 2008;38:1221–32.

    PubMed  CAS  Google Scholar 

  67. Das R, Roy A, Dutta N, Majumder HK. Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani. Apoptosis. 2008;13:867–82.

    Article  PubMed  CAS  Google Scholar 

  68. Freudlsperger C, Greten J, Schumacher U. Curcumin induces apoptosis in human neuroblastoma cells via inhibition of NFkappaB. Anticancer Res. 2008;28:209–14.

    PubMed  CAS  Google Scholar 

  69. Hail N Jr. Mitochondrial reactive oxygen species affect sensitivity to curcumin-induced apoptosis. Free Radic Biol Med. 2008;44:1382–93.

    Article  PubMed  CAS  Google Scholar 

  70. Hoque A, Chen H, Xu XC. Statin induces apoptosis and cell growth arrest in prostate cancer cells. Cancer Epidemiol Biomarkers Prev. 2008;17:88–94.

    Article  PubMed  CAS  Google Scholar 

  71. Zhu YG, Chen XC, Chen ZZ, et al. Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons. Acta Pharmacol Sin. 2004;25:1606–12.

    PubMed  CAS  Google Scholar 

  72. Kamath R, Jiang Z, Sun G, Yalowich JC, Baskaran R. c-Abl kinase regulates curcumin-induced cell death through activation of c-Jun N-terminal kinase. Mol Pharmacol. 2007;71:61–72.

    Article  PubMed  CAS  Google Scholar 

  73. Yang FW, Huang JZ, Lin XL, Zhen ZN, Chen XM. Apoptosis in nasopharyngeal carcinoma cell line NCE induced by curcumin and its molecular mechanism. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2006;41:612–6.

    PubMed  Google Scholar 

  74. Mosieniak G, Sliwinska M, Piwocka K, Sikora E. Curcumin abolishes apoptosis resistance of calcitriol-differentiated HL-60 cells. FEBS Lett. 2006;580:4653–60.

    Article  PubMed  CAS  Google Scholar 

  75. Wolanin K, Magalska A, Mosieniak G, et al. Curcumin affects components of the chromosomal passenger complex and induces mitotic catastrophe in apoptosis-resistant Bcr-Abl-expressing cells. Mol Cancer Res. 2006;4:457–69.

    Article  PubMed  CAS  Google Scholar 

  76. Deeb DD, Jiang H, Gao X, Divine G, Dulchavsky SA, Gautam SC. Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. J Exp Ther Oncol. 2005;5:81–91.

    PubMed  CAS  Google Scholar 

  77. Chen ZQ, Jie X, Mo ZN. Curcumin inhibits growth, induces G1 arrest and apoptosis on human prostatic stromal cells by regulating Bcl-2/Bax. Zhongguo Zhong Yao Za Zhi. 2008;33:2022–5.

    PubMed  CAS  Google Scholar 

  78. Watson JL, Hill R, Lee PW, Giacomantonio CA, Hoskin DW. Curcumin induces apoptosis in HCT-116 human colon cancer cells in a p21-independent manner. Exp Mol Pathol. 2008;84:230–3.

    Article  PubMed  CAS  Google Scholar 

  79. Mackenzie GG, Queisser N, Wolfson ML, Fraga CG, Adamo AM, Oteiza PI. Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells. Int J Cancer. 2008;123:56–65.

    Article  PubMed  CAS  Google Scholar 

  80. Kunnumakkara AB, Diagaradjane P, Guha S, et al. Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappaB-regulated gene products. Clin Cancer Res. 2008;14:2128–36.

    Article  PubMed  CAS  Google Scholar 

  81. Shankar S, Ganapathy S, Chen Q, Srivastava RK. Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis. Mol Cancer. 2008;7:16.

    Article  PubMed  CAS  Google Scholar 

  82. Walters DK, Muff R, Langsam B, Born W, Fuchs B. Cytotoxic effects of curcumin on osteosarcoma cell lines. Invest New Drugs. 2008;26:289–97.

    Article  PubMed  CAS  Google Scholar 

  83. Shankar S, Srivastava RK. Bax and Bak genes are essential for maximum apoptotic response by curcumin, a polyphenolic compound and cancer chemopreventive agent derived from turmeric, Curcuma longa. Carcinogenesis. 2007;28:1277–86.

    Article  PubMed  CAS  Google Scholar 

  84. Liu B, Bai QX, Chen XQ, Gao GX, Gu HT. Effect of curcumin on expression of survivin, Bcl-2 and Bax in human multiple myeloma cell line. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007;15:762–6.

    PubMed  CAS  Google Scholar 

  85. Sandur SK, Ichikawa H, Pandey MK, et al. Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects of curcumin (diferuloylmethane). Free Radic Biol Med. 2007;43:568–80.

    Article  PubMed  CAS  Google Scholar 

  86. Yu Z, Shah DM. Curcumin down-regulates Ets-1 and Bcl-2 expression in human endometrial carcinoma HEC-1-A cells. Gynecol Oncol. 2007;106:541–8.

    Article  PubMed  CAS  Google Scholar 

  87. Karunagaran D, Joseph J, Kumar TR. Cell growth regulation. Adv Exp Med Biol. 2007;595:245–68.

    Article  PubMed  Google Scholar 

  88. Karmakar S, Banik NL, Ray SK. Curcumin suppressed anti-apoptotic signals and activated cysteine proteases for apoptosis in human malignant glioblastoma U87MG cells. Neurochem Res. 2007;32:2103–13.

    Article  PubMed  CAS  Google Scholar 

  89. Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007;67:3853–61.

    Article  PubMed  CAS  Google Scholar 

  90. Bhattacharyya S, Mandal D, Saha B, Sen GS, Das T, Sa G. Curcumin prevents tumor-induced T cell apoptosis through Stat-5a-mediated Bcl-2 induction. J Biol Chem. 2007;282:15954–64.

    Article  PubMed  CAS  Google Scholar 

  91. Deeb D, Jiang H, Gao X, et al. Curcumin [1, 7-bis(4-hydroxy-3-methoxyphenyl)-1–6-heptadine-3, 5-dione; C21H20O6] sensitizes human prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand/Apo2L-induced apoptosis by suppressing nuclear factor-kappaB via inhibition of the prosurvival Akt signaling pathway. J Pharmacol Exp Ther. 2007;321:616–25.

    Article  PubMed  CAS  Google Scholar 

  92. Su CC, Chen GW, Lin JG, Wu LT, Chung JG. Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res. 2006;26:1281–8.

    PubMed  CAS  Google Scholar 

  93. Balasubramanian S, Eckert RL. Curcumin suppresses AP1 transcription factor-dependent differentiation and activates apoptosis in human epidermal keratinocytes. J Biol Chem. 2007;282:6707–15.

    Article  PubMed  CAS  Google Scholar 

  94. Chan WH, Wu HY, Chang WH. Dosage effects of curcumin on cell death types in a human osteoblast cell line. Food Chem Toxicol. 2006;44:1362–71.

    Article  PubMed  CAS  Google Scholar 

  95. Kwon Y, Magnuson BA. Age-related differential responses to curcumin-induced apoptosis during the initiation of colon cancer in rats. Food Chem Toxicol. 2009;47:377–85.

    Article  PubMed  CAS  Google Scholar 

  96. Ghoneim AI. Effects of curcumin on ethanol-induced hepatocyte necrosis and apoptosis: implication of lipid peroxidation and cytochrome c. Naunyn Schmiedebergs Arch Pharmacol. 2009;379:47–60.

    Article  PubMed  CAS  Google Scholar 

  97. Wang WZ, Cheng J, Luo J, Zhuang SM. Abrogation of G2/M arrest sensitizes curcumin-resistant hepatoma cells to apoptosis. FEBS Lett. 2008;582:2689–95.

    Article  PubMed  CAS  Google Scholar 

  98. Liao YF, Hung HC, Hour TC, et al. Curcumin induces apoptosis through an ornithine decarboxylase-dependent pathway in human promyelocytic leukemia HL-60 cells. Life Sci. 2008;82:367–75.

    PubMed  CAS  Google Scholar 

  99. Gopinath P, Ghosh SS. Apoptotic induction with bifunctional E. coli cytosine deaminase-uracil phosphoribosyltransferase mediated suicide gene therapy is synergized by curcumin treatment in vitro. Mol Biotechnol. 2008;39:39–48.

    Article  PubMed  CAS  Google Scholar 

  100. Wan XH, Luo XP. Relationship between copper injury and apoptosis and the effect of curcumin on copper-injured BRL cells. Zhongguo Dang Dai Er Ke Za Zhi. 2007;9:567–70.

    PubMed  CAS  Google Scholar 

  101. Raza H, John A, Brown EM, Benedict S, Kambal A. Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells. Toxicol Appl Pharmacol. 2008;226:161–8.

    Article  PubMed  CAS  Google Scholar 

  102. Cao J, Liu Y, Jia L, et al. Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells. Free Radic Biol Med. 2007;43:968–75.

    Article  PubMed  CAS  Google Scholar 

  103. Wahl H, Tan L, Griffith K, Choi M, Liu JR. Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer cells. Gynecol Oncol. 2007;105:104–12.

    Article  PubMed  CAS  Google Scholar 

  104. Balasubramanian S, Eckert RL. Keratinocyte proliferation, differentiation, and apoptosis-differential mechanisms of regulation by curcumin, EGCG and apigenin. Toxicol Appl Pharmacol. 2007;224:214–9.

    Article  PubMed  CAS  Google Scholar 

  105. Huang XR, Qi MX, Kang KR. Apoptosis of lens epithelial cell induced by curcumin and its mechanism. Zhonghua Yan Ke Za Zhi. 2006;42:649–53.

    PubMed  CAS  Google Scholar 

  106. Karmakar S, Banik NL, Patel SJ, Ray SK. Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic pathways for apoptosis in human glioblastoma T98G cells. Neurosci Lett. 2006;407:53–8.

    Article  PubMed  CAS  Google Scholar 

  107. Chan WH, Wu HJ. Protective effects of curcumin on methylglyoxal-induced oxidative DNA damage and cell injury in human mononuclear cells. Acta Pharmacol Sin. 2006;27:1192–8.

    Article  PubMed  CAS  Google Scholar 

  108. Chen J, Tang XQ, Zhi JL, et al. Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ion-induced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway. Apoptosis. 2006;11:943–53.

    Article  PubMed  CAS  Google Scholar 

  109. Banjerdpongchai R, Wilairat P. Effects of water-soluble antioxidants and MAPKK/MEK inhibitor on curcumin-induced apoptosis in HL-60 human leukemic cells. Asian Pac J Cancer Prev. 2005;6:282–5.

    PubMed  Google Scholar 

  110. Wang Q, Sun AY, Simonyi A, et al. Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J Neurosci Res. 2005;82:138–48.

    Article  PubMed  CAS  Google Scholar 

  111. Uddin S, Hussain AR, Manogaran PS, et al. Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma. Oncogene. 2005;24:7022–30.

    Article  PubMed  CAS  Google Scholar 

  112. Sen S, Sharma H, Singh N. Curcumin enhances Vinorelbine mediated apoptosis in NSCLC cells by the mitochondrial pathway. Biochem Biophys Res Commun. 2005;331:1245–52.

    Article  PubMed  CAS  Google Scholar 

  113. Karunagaran D, Rashmi R, Kumar TR. Induction of apoptosis by curcumin and its implications for cancer therapy. Curr Cancer Drug Targets. 2005;5:117–29.

    Article  PubMed  CAS  Google Scholar 

  114. Nair J, Strand S, Frank N, et al. Apoptosis and age-dependant induction of nuclear and mitochondrial etheno-DNA adducts in Long–Evans Cinnamon (LEC) rats: enhanced DNA damage by dietary curcumin upon copper accumulation. Carcinogenesis. 2005;26:1307–15.

    Article  PubMed  CAS  Google Scholar 

  115. Ligeret H, Barthelemy S, Zini R, Tillement JP, Labidalle S, Morin D. Effects of curcumin and curcumin derivatives on mitochondrial permeability transition pore. Free Radic Biol Med. 2004;36:919–29.

    Article  PubMed  CAS  Google Scholar 

  116. Jana NR, Dikshit P, Goswami A, Nukina N. Inhibition of proteasomal function by curcumin induces apoptosis through mitochondrial pathway. J Biol Chem. 2004;279:11680–5.

    Article  PubMed  CAS  Google Scholar 

  117. Morin D, Barthelemy S, Zini R, Labidalle S, Tillement JP. Curcumin induces the mitochondrial permeability transition pore mediated by membrane protein thiol oxidation. FEBS Lett. 2001;495:131–6.

    Article  PubMed  CAS  Google Scholar 

  118. Shinojima N, Yokoyama T, Kondo Y, Kondo S. Roles of the Akt/mTOR/p70S6K and ERK1/2 signaling pathways in curcumin-induced autophagy. Autophagy. 2007;3:635–7.

    PubMed  CAS  Google Scholar 

  119. Aoki H, Takada Y, Kondo S, Sawaya R, Aggarwal BB, Kondo Y. Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol Pharmacol. 2007;72:29–39.

    Article  PubMed  CAS  Google Scholar 

  120. Collett GP, Campbell FC. Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells. Carcinogenesis. 2006;27:1285–91.

    Article  PubMed  CAS  Google Scholar 

  121. Ramachandran C, Rodriguez S, Ramachandran R, et al. Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res. 2005;25:3293–302.

    PubMed  CAS  Google Scholar 

  122. Sawada H, Ibi M, Kihara T, et al. Estradiol protects dopaminergic neurons in a MPP + Parkinson's disease model. Neuropharmacology. 2002;42:1056–64.

    Article  PubMed  CAS  Google Scholar 

  123. Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002;62:3868–75.

    PubMed  CAS  Google Scholar 

  124. Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene. 2001;20:7597–609.

    Article  PubMed  CAS  Google Scholar 

  125. Rajasingh J, Raikwar HP, Muthian G, Johnson C, Bright JJ. Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia. Biochem Biophys Res Commun. 2006;340:359–68.

    Article  PubMed  CAS  Google Scholar 

  126. Kuttan G, Kumar KB, Guruvayoorappan C, Kuttan R. Antitumor, anti-invasion, and antimetastatic effects of curcumin. Adv Exp Med Biol. 2007;595:173–84.

    Article  PubMed  Google Scholar 

  127. Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol. 2006;69:195–206.

    PubMed  CAS  Google Scholar 

  128. Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D'Alessandro N. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Lett. 2005;224:53–65.

    PubMed  CAS  Google Scholar 

  129. Li L, Aggarwal BB, Shishodia S, Abbruzzese J, Kurzrock R. Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer. 2004;101:2351–62.

    Article  PubMed  CAS  Google Scholar 

  130. Park CH, Hahm ER, Park S, Kim HK, Yang CH. The inhibitory mechanism of curcumin and its derivative against beta-catenin/Tcf signaling. FEBS Lett. 2005;579:2965–71.

    Article  PubMed  CAS  Google Scholar 

  131. Jaiswal AS, Marlow BP, Gupta N, Narayan S. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene. 2002;21:8414–27.

    Article  PubMed  CAS  Google Scholar 

  132. Weir NM, Selvendiran K, Kutala VK, et al. Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol Ther. 2007;6:178–84.

    Article  PubMed  CAS  Google Scholar 

  133. Zheng M, Ekmekcioglu S, Walch ET, Tang CH, Grimm EA. Inhibition of nuclear factor-kappaB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. Melanoma Res. 2004;14:165–71.

    Article  PubMed  CAS  Google Scholar 

  134. Woo JH, Kim YH, Choi YJ, et al. Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis. 2003;24:1199–208.

    Article  PubMed  CAS  Google Scholar 

  135. Li M, Zhang Z, Hill DL, Wang H, Zhang R. Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. Cancer Res. 2007;67:1988–96.

    Article  PubMed  CAS  Google Scholar 

  136. Beevers CS, Chen L, Liu L, Luo Y, Webster NJ, Huang S. Curcumin disrupts the mammalian target of rapamycin-raptor complex. Cancer Res. 2009;69:1000–8.

    Article  PubMed  CAS  Google Scholar 

  137. Guo H, Yu JH, Chen K, Ye ZQ, Liu GC. Curcumin-induced apoptosis in androgen-dependent prostate cancer cell line LNCaP in vitro. Zhonghua Nan Ke Xue. 2006;12:141–4.

    PubMed  CAS  Google Scholar 

  138. Dorai T, Gehani N, Katz A. Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Prostate Cancer Prostatic Dis. 2000;3:84–93.

    Article  PubMed  CAS  Google Scholar 

  139. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate. 2001;47:293–303.

    Article  PubMed  CAS  Google Scholar 

  140. Nakamura K, Yasunaga Y, Segawa T, et al. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol. 2002;21:825–30.

    PubMed  CAS  Google Scholar 

  141. Lin JK. Suppression of protein kinase C and nuclear oncogene expression as possible action mechanisms of cancer chemoprevention by curcumin. Arch Pharm Res. 2004;27:683–92.

    Article  PubMed  CAS  Google Scholar 

  142. Lev-Ari S, Strier L, Kazanov D, et al. Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells. Rheumatology (Oxford). 2006;45:171–7.

    Article  CAS  Google Scholar 

  143. Squires MS, Hudson EA, Howells L, et al. Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochem Pharmacol. 2003;65:361–76.

    Article  PubMed  CAS  Google Scholar 

  144. Chadalapaka G, Jutooru I, Chintharlapalli S, et al. Curcumin decreases specificity protein expression in bladder cancer cells. Cancer Res. 2008;68:5345–54.

    Article  PubMed  CAS  Google Scholar 

  145. Pan W, Yang H, Cao C, et al. AMPK mediates curcumin-induced cell death in CaOV3 ovarian cancer cells. Oncol Rep. 2008;20:1553–9.

    PubMed  CAS  Google Scholar 

  146. Swamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Nutr Cancer. 2008;60(Suppl 1):81–9.

    Article  PubMed  CAS  Google Scholar 

  147. Park C, Moon DO, Choi IW, et al. Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis. Int J Mol Med. 2007;20:365–72.

    PubMed  CAS  Google Scholar 

  148. Lev-Ari S, Starr A, Vexler A, et al. Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res. 2006;26:4423–30.

    PubMed  CAS  Google Scholar 

  149. Atsumi T, Murakami Y, Shibuya K, Tonosaki K, Fujisawa S. Induction of cytotoxicity and apoptosis and inhibition of cyclooxygenase-2 gene expression, by curcumin and its analog, alpha-diisoeugenol. Anticancer Res. 2005;25:4029–36.

    PubMed  CAS  Google Scholar 

  150. Shishodia S, Amin HM, Lai R, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol. 2005;70:700–13.

    Article  PubMed  CAS  Google Scholar 

  151. Leu TH, Maa MC. The molecular mechanisms for the antitumorigenic effect of curcumin. Curr Med Chem Anticancer Agents. 2002;2:357–70.

    Article  PubMed  CAS  Google Scholar 

  152. Cheng Y, Kozubek A, Ohlsson L, Sternby B, Duan RD. Curcumin decreases acid sphingomyelinase activity in colon cancer Caco-2 cells. Planta Med. 2007;73:725–30.

    Article  PubMed  CAS  Google Scholar 

  153. Moussavi M, Assi K, Gomez-Munoz A, Salh B. Curcumin mediates ceramide generation via the de novo pathway in colon cancer cells. Carcinogenesis. 2006;27:1636–44.

    Article  PubMed  CAS  Google Scholar 

  154. Yamamoto H, Hanada K, Kawasaki K, Nishijima M. Inhibitory effect on curcumin on mammalian phospholipase D activity. FEBS Lett. 1997;417:196–8.

    Article  PubMed  CAS  Google Scholar 

  155. Adams BK, Cai J, Armstrong J, et al. EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs. 2005;16:263–75.

    Article  PubMed  CAS  Google Scholar 

  156. Fang J, Lu J, Holmgren A. Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J Biol Chem. 2005;280:25284–90.

    Article  PubMed  CAS  Google Scholar 

  157. Liu Z, Du ZY, Huang ZS, Lee KS, Gu LQ. Inhibition of thioredoxin reductase by curcumin analogs. Biosci Biotechnol Biochem. 2008;72:2214–8.

    Article  PubMed  CAS  Google Scholar 

  158. Marcu MG, Jung YJ, Lee S, et al. Curcumin is an inhibitor of p300 histone acetylatransferase. Med Chem. 2006;2:169–74.

    Article  PubMed  CAS  Google Scholar 

  159. Hu J, Wang Y, Chen Y. Curcumin-induced histone acetylation in malignant hematologic cells. J Huazhong Univ Sci Technolog Med Sci. 2009;29:25–8.

    PubMed  CAS  Google Scholar 

  160. Bakhshi J, Weinstein L, Poksay KS, Nishinaga B, Bredesen DE, Rao RV. Coupling endoplasmic reticulum stress to the cell death program in mouse melanoma cells: effect of curcumin. Apoptosis. 2008;13:904–14.

    Article  PubMed  CAS  Google Scholar 

  161. Bentzen PJ, Lang E, Lang F. Curcumin induced suicidal erythrocyte death. Cell Physiol Biochem. 2007;19:153–64.

    Article  PubMed  CAS  Google Scholar 

  162. Bae JH, Park JW, Kwon TK. Ruthenium red, inhibitor of mitochondrial Ca2+ uniporter, inhibits curcumin-induced apoptosis via the prevention of intracellular Ca2+ depletion and cytochrome c release. Biochem Biophys Res Commun. 2003;303:1073–9.

    Article  PubMed  CAS  Google Scholar 

  163. Santel T, Pflug G, Hemdan NY, et al. Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity. PLoS ONE. 2008;3:e3508.

    Article  PubMed  CAS  Google Scholar 

  164. Choudhary D, Chandra D, Kale RK. Modulation of radioresponse of glyoxalase system by curcumin. J Ethnopharmacol. 1999;64:1–7.

    Article  PubMed  CAS  Google Scholar 

  165. Gupta KK, Bharne SS, Rathinasamy K, Naik NR, Panda D. Dietary antioxidant curcumin inhibits microtubule assembly through tubulin binding. Febs J. 2006;273:5320–32.

    Article  PubMed  CAS  Google Scholar 

  166. Dempe JS, Pfeiffer E, Grimm AS, Metzler M. Metabolism of curcumin and induction of mitotic catastrophe in human cancer cells. Mol Nutr Food Res. 2008;52:1074–81.

    Article  PubMed  CAS  Google Scholar 

  167. Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res. 2008;68:7283–92.

    Article  PubMed  CAS  Google Scholar 

  168. Yang H, Landis-Piwowar KR, Chen D, Milacic V, Dou QP. Natural compounds with proteasome inhibitory activity for cancer prevention and treatment. Curr Protein Pept Sci. 2008;9:227–39.

    Article  PubMed  CAS  Google Scholar 

  169. Dikshit P, Goswami A, Mishra A, Chatterjee M, Jana NR. Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB activation by inhibiting the proteasome function. Neurotox Res. 2006;9:29–37.

    Article  PubMed  CAS  Google Scholar 

  170. Wan XH, Li YW, Luo XP. Curcumin attenuated the lipid peroxidation and apoptotic liver injury in copper-overloaded rats. Zhonghua Er Ke Za Zhi. 2007;45:604–8.

    PubMed  Google Scholar 

  171. Yoshino M, Haneda M, Naruse M, et al. Prooxidant activity of curcumin: copper-dependent formation of 8-hydroxy-2'-deoxyguanosine in DNA and induction of apoptotic cell death. Toxicol In Vitro. 2004;18:783–9.

    Article  PubMed  CAS  Google Scholar 

  172. Syng-Ai C, Kumari AL, Khar A. Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther. 2004;3:1101–8.

    PubMed  CAS  Google Scholar 

  173. Jaruga E, Bielak-Zmijewska A, Sikora E, et al. Glutathione-independent mechanism of apoptosis inhibition by curcumin in rat thymocytes. Biochem Pharmacol. 1998;56:961–5.

    Article  PubMed  CAS  Google Scholar 

  174. William BM, Goodrich A, Peng C, Li S. Curcumin inhibits proliferation and induces apoptosis of leukemic cells expressing wild-type or T315I-BCR-ABL and prolongs survival of mice with acute lymphoblastic leukemia. Hematology. 2008;13:333–43.

    Article  PubMed  CAS  Google Scholar 

  175. Hussain AR, Al-Rasheed M, Manogaran PS, et al. Curcumin induces apoptosis via inhibition of PI3'-kinase/AKT pathway in acute T cell leukemias. Apoptosis. 2006;11:245–54.

    Article  PubMed  CAS  Google Scholar 

  176. Du J, Suzuki H, Nagase F, et al. Methylglyoxal induces apoptosis in Jurkat leukemia T cells by activating c-Jun N-terminal kinase. J Cell Biochem. 2000;77:333–44.

    Article  PubMed  CAS  Google Scholar 

  177. Chen Y, Wu Y, He J, Chen W. The experimental and clinical study on the effect of curcumin on cell cycle proteins and regulating proteins of apoptosis in acute myelogenous leukemia. J Huazhong Univ Sci Technolog Med Sci. 2002;22:295–8.

    PubMed  CAS  Google Scholar 

  178. Pae HO, Jeong SO, Jeong GS, et al. Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells. Biochem Biophys Res Commun. 2007;353:1040–5.

    Article  PubMed  CAS  Google Scholar 

  179. Mukherjee Nee Chakraborty S, Ghosh U, Bhattacharyya NP, Bhattacharya RK, Dey S, Roy M. Curcumin-induced apoptosis in human leukemia cell HL-60 is associated with inhibition of telomerase activity. Mol Cell Biochem. 2007;297:31–9.

    Article  PubMed  CAS  Google Scholar 

  180. Roy M, Chakraborty S, Siddiqi M, Bhattacharya RK. Induction of apoptosis in tumor cells by natural phenolic compounds. Asian Pac J Cancer Prev. 2002;3:61–7.

    PubMed  Google Scholar 

  181. Duvoix A, Morceau F, Schnekenburger M, et al. Curcumin-induced cell death in two leukemia cell lines: K562 and Jurkat. Ann N Y Acad Sci. 2003;1010:389–92.

    Article  PubMed  CAS  Google Scholar 

  182. Sun C, Liu X, Chen Y, Liu F. Anticancer effect of curcumin on human B cell non-Hodgkin's lymphoma. J Huazhong Univ Sci Technolog Med Sci. 2005;25:404–7.

    PubMed  CAS  Google Scholar 

  183. Skommer J, Wlodkowic D, Pelkonen J. Cellular foundation of curcumin-induced apoptosis in follicular lymphoma cell lines. Exp Hematol. 2006;34:463–74.

    Article  PubMed  CAS  Google Scholar 

  184. Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood. 2003;101:1053–62.

    Article  PubMed  CAS  Google Scholar 

  185. Bharti AC, Shishodia S, Reuben JM, et al. Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood. 2004;103:3175–84.

    Article  PubMed  CAS  Google Scholar 

  186. Tian F, Song M, Xu PR, Liu HT, Xue LX. Curcumin promotes apoptosis of esophageal squamous carcinoma cell lines through inhibition of NF-kappaB signaling pathway. Ai Zheng. 2008;27:566–70.

    PubMed  CAS  Google Scholar 

  187. Collett GP, Robson CN, Mathers JC, Campbell FC. Curcumin modifies Apc(min) apoptosis resistance and inhibits 2-amino 1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) induced tumour formation in Apc(min) mice. Carcinogenesis. 2001;22:821–5.

    Article  PubMed  CAS  Google Scholar 

  188. Huang AC, Lin SY, Su CC, et al. Effects of curcumin on N-bis(2-hydroxypropyl) nitrosamine (DHPN)-induced lung and liver tumorigenesis in BALB/c mice in vivo. In Vivo. 2008;22:781–5.

    PubMed  CAS  Google Scholar 

  189. Priya S, Sudhakaran PR. Curcumin-induced recovery from hepatic injury involves induction of apoptosis of activated hepatic stellate cells. Indian J Biochem Biophys. 2008;45:317–25.

    PubMed  CAS  Google Scholar 

  190. Chan WH, Wu HJ, Hsuuw YD. Curcumin inhibits ROS formation and apoptosis in methylglyoxal-treated human hepatoma G2 cells. Ann N Y Acad Sci. 2005;1042:372–8.

    Article  PubMed  CAS  Google Scholar 

  191. Khar A, Ali AM, Pardhasaradhi BV, Varalakshmi CH, Anjum R, Kumari AL. Induction of stress response renders human tumor cell lines resistant to curcumin-mediated apoptosis: role of reactive oxygen intermediates. Cell Stress Chaperones. 2001;6:368–76.

    Article  PubMed  CAS  Google Scholar 

  192. Hsu YC, Weng HC, Lin S, Chien YW. Curcuminoids-cellular uptake by human primary colon cancer cells as quantitated by a sensitive HPLC assay and its relation with the inhibition of proliferation and apoptosis. J Agric Food Chem. 2007;55:8213–22.

    Article  PubMed  CAS  Google Scholar 

  193. Lev-Ari S, Maimon Y, Strier L, Kazanov D, Arber N. Down-regulation of prostaglandin E2 by curcumin is correlated with inhibition of cell growth and induction of apoptosis in human colon carcinoma cell lines. J Soc Integr Oncol. 2006;4:21–6.

    PubMed  Google Scholar 

  194. Scott DW, Loo G. Curcumin-induced GADD153 gene up-regulation in human colon cancer cells. Carcinogenesis. 2004;25:2155–64.

    Article  PubMed  CAS  Google Scholar 

  195. Collett GP, Campbell FC. Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells. Carcinogenesis. 2004;25:2183–9.

    Article  PubMed  CAS  Google Scholar 

  196. Rashmi R, Kumar S, Karunagaran D. Ectopic expression of Hsp70 confers resistance and silencing its expression sensitizes human colon cancer cells to curcumin-induced apoptosis. Carcinogenesis. 2004;25:179–87.

    Article  PubMed  CAS  Google Scholar 

  197. Moragoda L, Jaszewski R, Majumdar AP. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res. 2001;21:873–8.

    PubMed  CAS  Google Scholar 

  198. Chen H, Zhang ZS, Zhang YL, Zhou DY. Curcumin inhibits cell proliferation by interfering with the cell cycle and inducing apoptosis in colon carcinoma cells. Anticancer Res. 1999;19:3675–80.

    PubMed  CAS  Google Scholar 

  199. Kamat AM, Sethi G, Aggarwal BB. Curcumin potentiates the apoptotic effects of chemotherapeutic agents and cytokines through down-regulation of nuclear factor-kappaB and nuclear factor-kappaB-regulated gene products in IFN-alpha-sensitive and IFN-alpha-resistant human blad. Mol Cancer Ther. 2007;6:1022–30.

    Article  PubMed  CAS  Google Scholar 

  200. Tong QS, Zheng LD, Lu P, et al. Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells. Anticancer Drugs. 2006;17:279–87.

    Article  PubMed  CAS  Google Scholar 

  201. Deeb D, Jiang H, Gao X, et al. Curcumin sensitizes prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand/Apo2L by inhibiting nuclear factor-kappaB through suppression of IkappaBalpha phosphorylation. Mol Cancer Ther. 2004;3:803–12.

    PubMed  CAS  Google Scholar 

  202. Andrzejewski T, Deeb D, Gao X, et al. Therapeutic efficacy of curcumin/TRAIL combination regimen for hormone-refractory prostate cancer. Oncol Res. 2008;17:257–67.

    Article  PubMed  CAS  Google Scholar 

  203. Chendil D, Ranga RS, Meigooni D, Sathishkumar S, Ahmed MM. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene. 2004;23:1599–607.

    Article  PubMed  CAS  Google Scholar 

  204. Deeb D, Xu YX, Jiang H, et al. Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther. 2003;2:95–103.

    PubMed  CAS  Google Scholar 

  205. Antonio AM, Druse MJ. Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons. Brain Res. 2008;1204:16–23.

    Article  PubMed  CAS  Google Scholar 

  206. Aravindan N, Madhusoodhanan R, Ahmad S, Johnson D, Herman TS. Curcumin inhibits NFkappaB mediated radioprotection and modulate apoptosis related genes in human neuroblastoma cells. Cancer Biol Ther. 2008;7:569–76.

    Article  PubMed  CAS  Google Scholar 

  207. Belkaid A, Copland IB, Massillon D, Annabi B. Silencing of the human microsomal glucose-6-phosphate translocase induces glioma cell death: potential new anticancer target for curcumin. FEBS Lett. 2006;580:3746–52.

    Article  PubMed  CAS  Google Scholar 

  208. Khajavi M, Inoue K, Wiszniewski W, Ohyama T, Snipes GJ, Lupski JR. Curcumin treatment abrogates endoplasmic reticulum retention and aggregation-induced apoptosis associated with neuropathy-causing myelin protein zero-truncating mutants. Am J Hum Genet. 2005;77:841–50.

    Article  PubMed  CAS  Google Scholar 

  209. Nagai S, Kurimoto M, Washiyama K, Hirashima Y, Kumanishi T, Endo S. Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. J Neurooncol. 2005;74:105–11.

    Article  PubMed  CAS  Google Scholar 

  210. Kim HI, Huang H, Cheepala S, Huang S, Chung J. Curcumin inhibition of integrin (alpha6beta4)-dependent breast cancer cell motility and invasion. Cancer Prev Res (Phila Pa). 2008;1:385–91.

    CAS  Google Scholar 

  211. Aggarwal BB, Shishodia S, Takada Y, et al. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res. 2005;11:7490–8.

    Article  PubMed  CAS  Google Scholar 

  212. Kim MS, Kang HJ, Moon A. Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCF10A human breast epithelial cells. Arch Pharm Res. 2001;24:349–54.

    Article  PubMed  CAS  Google Scholar 

  213. Zheng LD, Tong QS, Wu CH. Inhibitory effects of curcumin on apoptosis of human ovary cancer cell line A2780 and its molecular mechanism. Ai Zheng. 2002;21:1296–300.

    PubMed  Google Scholar 

  214. Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP, Carrier E. Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett. 2004;208:163–70.

    Article  PubMed  CAS  Google Scholar 

  215. Tourkina E, Gooz P, Oates JC, Ludwicka-Bradley A, Silver RM, Hoffman S. Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon. Am J Respir Cell Mol Biol. 2004;31:28–35.

    Article  PubMed  CAS  Google Scholar 

  216. Marin YE, Wall BA, Wang S, et al. Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Melanoma Res. 2007;17:274–83.

    Article  PubMed  CAS  Google Scholar 

  217. Jang YH, Namkoong S, Kim YM, Lee SJ, Park BJ, Min DS. Cleavage of phospholipase D1 by caspase promotes apoptosis via modulation of the p53-dependent cell death pathway. Cell Death Differ. 2008;15:1782–93.

    Article  PubMed  CAS  Google Scholar 

  218. Furusu A, Nakayama K, Xu Q, Konta T, Kitamura M. MAP kinase-dependent, NF-kappaB-independent regulation of inhibitor of apoptosis protein genes by TNF-alpha. J Cell Physiol. 2007;210:703–10.

    Article  PubMed  CAS  Google Scholar 

  219. Magalska A, Sliwinska M, Szczepanowska J, Salvioli S, Franceschi C, Sikora E. Resistance to apoptosis of HCW-2 cells can be overcome by curcumin- or vincristine-induced mitotic catastrophe. Int J Cancer. 2006;119:1811–8.

    Article  PubMed  CAS  Google Scholar 

  220. Bielak-Zmijewska A, Koronkiewicz M, Skierski J, Piwocka K, Radziszewska E, Sikora E. Effect of curcumin on the apoptosis of rodent and human nonproliferating and proliferating lymphoid cells. Nutr Cancer. 2000;38:131–8.

    Article  PubMed  CAS  Google Scholar 

  221. Scharstuhl A, Mutsaers HA, Pennings SW, Szarek WA, Russel FG, Wagener FA (2008) Curcumin-Induced Fibroblast Apoptosis and in Vitro Wound Contraction Are Regulated by Antioxidants and Heme Oxygenase: Implications for Scar Formation. J Cell Mol Med

  222. Javvadi P, Segan AT, Tuttle SW, Koumenis C. The chemopreventive agent curcumin is a potent radiosensitizer of human cervical tumor cells via increased reactive oxygen species production and overactivation of the mitogen-activated protein kinase pathway. Mol Pharmacol. 2008;73:1491–501.

    Article  PubMed  CAS  Google Scholar 

  223. Zhang M, Bian F, Wen C, Hao N. Inhibitory effect of curcumin on proliferation of human pterygium fibroblasts. J Huazhong Univ Sci Technolog Med Sci. 2007;27:339–42.

    Article  PubMed  CAS  Google Scholar 

  224. Cucuzza LS, Motta M, Miretti S, Accornero P, Baratta M. Curcuminoid-phospholipid complex induces apoptosis in mammary epithelial cells by STAT-3 signaling. Exp Mol Med. 2008;40:647–57.

    Article  PubMed  CAS  Google Scholar 

  225. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB. Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis. 2002;23:143–50.

    Article  PubMed  CAS  Google Scholar 

  226. Agarwal ML, Taylor WR, Chernov MV, Chernova OB, Stark GR. The p53 network. J Biol Chem. 1998;273:1–4.

    Article  PubMed  CAS  Google Scholar 

  227. Ko LJ, Prives C. p53: puzzle and paradigm. Genes Dev. 1996;10:1054–72.

    Article  PubMed  CAS  Google Scholar 

  228. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell. 1997;88:323–31.

    Article  PubMed  CAS  Google Scholar 

  229. Sun Y, Oberley LW. Redox regulation of transcriptional activators. Free Radic Biol Med. 1996;21:335–48.

    Article  PubMed  CAS  Google Scholar 

  230. Lorenzo HK, Susin SA. Mitochondrial effectors in caspase-independent cell death. FEBS Lett. 2004;557:14–20.

    Article  PubMed  CAS  Google Scholar 

  231. Park MJ, Kim EH, Park IC, et al. Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53. Int J Oncol. 2002;21:379–83.

    PubMed  CAS  Google Scholar 

  232. Aggarwal BB, Banerjee S, Bharadwaj U, Sung B, Shishodia S, Sethi G. Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol. 2007;73:1024–32.

    Article  PubMed  CAS  Google Scholar 

  233. Sahu RP, Batra S, Srivastava SK. Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells. Br J Cancer. 2009;100:1425–33.

    Article  PubMed  CAS  Google Scholar 

  234. Yu S, Shen G, Khor TO, Kim JH, Kong AN. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther. 2008;7:2609–20.

    Article  PubMed  CAS  Google Scholar 

  235. Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer. 2005;104:879–90.

    Article  PubMed  CAS  Google Scholar 

  236. Plummer SM, Holloway KA, Manson MM, et al. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene. 1999;18:6013–20.

    Article  PubMed  CAS  Google Scholar 

  237. Rao CV. Regulation of COX and LOX by curcumin. Adv Exp Med Biol. 2007;595:213–26.

    Article  PubMed  Google Scholar 

  238. Suh Y, Afaq F, Johnson JJ, Mukhtar H. A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kappaB-signaling pathways. Carcinogenesis. 2009;30:300–7.

    Article  PubMed  CAS  Google Scholar 

  239. Okazaki Y, Iqbal M, Okada S. Suppressive effects of dietary curcumin on the increased activity of renal ornithine decarboxylase in mice treated with a renal carcinogen, ferric nitrilotriacetate. Biochim Biophys Acta. 2005;1740:357–66.

    PubMed  CAS  Google Scholar 

  240. Blasius R, Reuter S, Henry E, Dicato M, Diederich M. Curcumin regulates signal transducer and activator of transcription (STAT) expression in K562 cells. Biochem Pharmacol. 2006;72:1547–54.

    Article  PubMed  CAS  Google Scholar 

  241. Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol. 2003;171:3863–71.

    PubMed  CAS  Google Scholar 

  242. Huang TS, Lee SC, Lin JK. Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc Natl Acad Sci U S A. 1991;88:5292–6.

    Article  PubMed  CAS  Google Scholar 

  243. Suh HW, Kang S, Kwon KS. Curcumin attenuates glutamate-induced HT22 cell death by suppressing MAP kinase signaling. Mol Cell Biochem. 2007;298:187–94.

    Article  PubMed  CAS  Google Scholar 

  244. Cipriani B, Borsellino G, Knowles H, et al. Curcumin inhibits activation of Vgamma9Vdelta2 T cells by phosphoantigens and induces apoptosis involving apoptosis-inducing factor and large scale DNA fragmentation. J Immunol. 2001;167:3454–62.

    PubMed  CAS  Google Scholar 

  245. Cao J, Jia L, Zhou HM, Liu Y, Zhong LF. Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells. Toxicol Sci. 2006;91:476–83.

    Article  PubMed  CAS  Google Scholar 

  246. Lu HF, Yang JS, Lai KC et al (2009) Curcumin-Induced DNA Damage and Inhibited DNA Repair Genes Expressions in Mouse-Rat Hybrid Retina Ganglion Cells (N18). Neurochem Res

  247. Chen YC, Kuo TC, Lin-Shiau SY, Lin JK. Induction of HSP70 gene expression by modulation of Ca(+2) ion and cellular p53 protein by curcumin in colorectal carcinoma cells. Mol Carcinog. 1996;17:224–34.

    Article  PubMed  Google Scholar 

  248. Dean EJ, Ranson M, Blackhall F, Holt SV, Dive C. Novel therapeutic targets in lung cancer: Inhibitor of apoptosis proteins from laboratory to clinic. Cancer Treat Rev. 2007;33:203–12.

    Article  PubMed  CAS  Google Scholar 

  249. Bava SV, Puliappadamba VT, Deepti A, Nair A, Karunagaran D, Anto RJ. Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-kappaB and the serine/threonine kinase Akt and is independent of tubulin polymerization. J Biol Chem. 2005;280:6301–8.

    Article  PubMed  CAS  Google Scholar 

  250. Lin YG, Kunnumakkara AB, Nair A, et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res. 2007;13:3423–30.

    Article  PubMed  CAS  Google Scholar 

  251. Bhattacharyya S, Mandal D, Sen GS, et al. Tumor-induced oxidative stress perturbs nuclear factor-kappaB activity-augmenting tumor necrosis factor-alpha-mediated T-cell death: protection by curcumin. Cancer Res. 2007;67:362–70.

    Article  PubMed  CAS  Google Scholar 

  252. Shi Y, He B, Kuchenbecker KM, et al. Inhibition of Wnt-2 and galectin-3 synergistically destabilizes beta-catenin and induces apoptosis in human colorectal cancer cells. Int J Cancer. 2007;121:1175–81.

    Article  PubMed  CAS  Google Scholar 

  253. McNally SJ, Harrison EM, Ross JA, Garden OJ, Wigmore SJ. Curcumin induces heme oxygenase 1 through generation of reactive oxygen species, p38 activation and phosphatase inhibition. Int J Mol Med. 2007;19:165–72.

    PubMed  CAS  Google Scholar 

  254. Pae HO, Jeong GS, Jeong SO, et al. Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells. Exp Mol Med. 2007;39:267–77.

    PubMed  CAS  Google Scholar 

  255. Ramachandran C, Fonseca HB, Jhabvala P, Escalon EA, Melnick SJ. Curcumin inhibits telomerase activity through human telomerase reverse transcritpase in MCF-7 breast cancer cell line. Cancer Lett. 2002;184:1–6.

    Article  PubMed  CAS  Google Scholar 

  256. Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI. Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochim Biophys Acta. 2008;1780:673–9.

    PubMed  CAS  Google Scholar 

  257. Premanand C, Rema M, Sameer MZ, Sujatha M, Balasubramanyam M. Effect of curcumin on proliferation of human retinal endothelial cells under in vitro conditions. Invest Ophthalmol Vis Sci. 2006;47:2179–84.

    Article  PubMed  Google Scholar 

  258. Magalska A, Brzezinska A, Bielak-Zmijewska A, Piwocka K, Mosieniak G, Sikora E. Curcumin induces cell death without oligonucleosomal DNA fragmentation in quiescent and proliferating human CD8+ cells. Acta Biochim Pol. 2006;53:531–8.

    PubMed  CAS  Google Scholar 

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ACKNOWLEDGMENTS

We thank Walter Pagel for carefully proofreading the manuscript and providing valuable comments. Dr. Aggarwal is Ransom Horne, Jr., Professor of Cancer Research. This work was supported by a grant from the Clayton Foundation for Research (B.B.A.), a core grant from the National Institutes of Health (CA-16 672), a program project grant from National Institutes of Health (NIH CA-124787-01A2), and grant from Center for Targeted Therapy of M.D. Anderson Cancer Center.

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  1. Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, BOX 143, Houston, TX, 77030, USA

    Jayaraj Ravindran, Sahdeo Prasad & Bharat B. Aggarwal

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  1. Jayaraj Ravindran
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  2. Sahdeo Prasad
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  3. Bharat B. Aggarwal
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Correspondence to Bharat B. Aggarwal.

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Ravindran, J., Prasad, S. & Aggarwal, B.B. Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?. AAPS J 11, 495–510 (2009). https://doi.org/10.1208/s12248-009-9128-x

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