Skip to main content
SpringerLink
Log in

CELL GROWTH REGULATION

  • Chapter
The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease

Part of the book series: ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY ((AEMB,volume 595))

Abstract

Curcumin, the active ingredient of turmeric (Curcuma longa) used in culinary and medical practices in Asia, has immense potential for being used in cancer chemotherapy because of its control over the cell growth regulatory mechanisms. The present chapter throws light on the role of curcumin in modulating the various phases of the cell cycle and its apoptosis-inducing effects. This is followed by a discussion on the implications of these effects of curcumin for its use as a chemotherapeutic agent in cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1. S. Shishodia, G. Sethi, and B. B. Aggarwal, Curcumin: getting back to the roots. Ann NY Acad Sci 1056, 206–217 (2005).

    Article  PubMed  CAS  Google Scholar 

  2. 2. R. K. Maheshwari, A. K. Singh, J. Gaddipati, and R. C. Srimal, Multiple biological activities of curcumin: A short review. Life Sci 78, 2081–2087 (2006).

    Article  PubMed  CAS  Google Scholar 

  3. 3. M. Notoya, H. Nishimura, J. T. Woo, K. Nagai, Y. Ishihara, and H. Hagiwara, Curcumin inhibits the proliferation and mineralization of cultured osteoblasts. Eur J Pharmacol 534, 55–62 (2006).

    Article  PubMed  CAS  Google Scholar 

  4. 4. J. S. Shim, J. Lee, H. J. Park, S. J. Park, and H. J. Kwon, A new curcumin derivative, HBC, interferes with the cell cycle progression of colon cancer cells via antagonization of the Ca2+/calmodulin function. Chem Biol 11, 1455–1463 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. 5. T. Choudhuri, S. Pal, T. Das, and G. Sa, Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem 280, 20,059–20,068 (2005).

    Article  CAS  Google Scholar 

  6. 6. Y. K. Kwon, J. M. Jun, S. W. Shin, J. W. Cho, and S. I. Suh, Curcumin decreases cell proliferation rates through BTG2-mediated cyclin D1 down-regulation in U937 cells. Int J Oncol 26, 1597–1603 (2005).

    PubMed  CAS  Google Scholar 

  7. 7. A. Chen and J. Xu, Activation of PPARγ by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR. Am J Physiol Gastrointest Liver Physiol 288, G447–G456 (2005).

    Article  PubMed  CAS  Google Scholar 

  8. 8. B. K. Batth, R. Tripathi and U. K. Srinivas, Curcumin-induced differentiation of mouse embryonal carcinoma PCC4 cells. Differentiation 68, 133–140 (2001).

    Article  PubMed  CAS  Google Scholar 

  9. 9. F. Shen, X. Fan, B. Liu, X. Jia, H. Du, B. You, M. Ye, C. Huang, and X. Shi, Overexpression of cyclin D1-CDK4 in silica-induced transformed cells is due to activation of ERKs, JNKs/AP-1 pathway. Toxicol Lett 160, 185–195 (2006).

    Article  PubMed  CAS  Google Scholar 

  10. 10. M. Tomita, H. Kawakami, J. N. Uchihara, T. Okudaira, M. Masuda, N. Takasu, T. Matsuda, T. Ohta, Y. Tanaka, K. Ohshiro, and N. Mori, Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells. Int J Cancer 118, 765–772 (2006).

    Article  PubMed  CAS  Google Scholar 

  11. 11. M. Sun, Y. Yang, H. Li, B. Su, Y. Lu, Q. Wei, and T. Fan, [The effect of curcumin on bladder cancer cell line EJ in vitro]. Zhong Yao Cai 27, 848–850 (2004).

    PubMed  Google Scholar 

  12. 12. S. Shishodia, P. Potdar, C. G. Gairola, and B. B. Aggarwal, Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis 24, 1269–1279 (2003).

    Article  PubMed  CAS  Google Scholar 

  13. 13. A. C. Bharti, N. Donato, S. Singh, and B. B. Aggarwal, 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 101, 1053–1062 (2003).

    Article  PubMed  CAS  Google Scholar 

  14. 14. A. K. Singh, G. S. Sidhu, T. Deepa, and R. K. Maheshwari, Curcumin inhibits the proliferation and cell cycle progression of human umbilical vein endothelial cell. Cancer Lett 107, 109–115 (1996).

    Article  PubMed  CAS  Google Scholar 

  15. 15. H. W. Chen and H. C. Huang, Effect of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells. Br J Pharmacol 124, 1029–1040 (1998).

    Article  PubMed  CAS  Google Scholar 

  16. 16. Y. Wu, Y. Chen, J. Xu, and L. Lu, Anticancer activities of curcumin on human Burkitt's lymphoma. Zhonghua Zhong Liu Za Zhi 24, 348–352 (2002).

    PubMed  Google Scholar 

  17. 17. S. Aggarwal, Y. Takada, S. Singh, J. N. Myers, and B. B. Aggarwal, Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-kappaB signaling. Int J Cancer 111, 679–692 (2004).

    Article  PubMed  CAS  Google Scholar 

  18. 18. S. Shishodia, H. M. Amin, R. Lai, and B. B. Aggarwal, Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol 70, 700–713 (2005).

    Article  PubMed  CAS  Google Scholar 

  19. 19. H. Chen, Z. S. Zhang, Y. L. Zhang, and D. Y. Zhou, Curcumin inhibits cell proliferation by interfering with the cell cycle and inducing apoptosis in colon carcinoma cells. Anticancer Res 19, 3675–3680 (1999).

    PubMed  CAS  Google Scholar 

  20. 20. D. Morin, S. Barthelemy, R. Zini, S. Labidalle, and J. P. Tillement, Curcumin induces the mitochondrial permeability transition pore mediated by membrane protein thiol oxidation. FEBS Lett 495, 131–136 (2001).

    Article  PubMed  CAS  Google Scholar 

  21. 21. M. Zheng, S. Ekmekcioglu, E. T. Walch, C. H. Tang, and E. A. Grimm, Inhibition of nuclear factor-kappaB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. Melanoma Res 14, 165–171 (2004).

    Article  PubMed  CAS  Google Scholar 

  22. 22. M. J. Van Erk, E. Teuling, Y. C. Staal, S. Huybers, P. J. Van Bladeren, J. M. Aarts, and B. Van Ommen, Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells. J Carcinog 3, 8 (2004).

    Article  PubMed  Google Scholar 

  23. 23. A. S. Jaiswal, B P. Marlow, N. Gupta, and S. Narayan, Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21, 8414–8427 (2002).

    Article  PubMed  CAS  Google Scholar 

  24. 24. A. Khafif, R. Hurst, K. Kyker, D. M. Fliss, Z. Gil, and J. E. Medina, Curcumin: A new radio-sensitizer of squamous cell carcinoma cells. Otolaryngol Head Neck Surg 132, 317–321 (2005).

    Article  PubMed  Google Scholar 

  25. 25. J. M. Holy, Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells. Mutat Res 518, 71–84 (2002).

    PubMed  CAS  Google Scholar 

  26. 26. C. Yan, M. S. Jamaluddin, B. Aggarwal, J. Myers, and D. D. Boyd, Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther 4, 233–241 (2005).

    PubMed  CAS  Google Scholar 

  27. 27. C. Ramachandran, H. B. Fonseca, P. Jhabvala, E. A. Escalon, and S. J. Melnick, Curcumin inhibits telomerase activity through human telomerase reverse transcritpase in MCF-7 breast cancer cell line. Cancer Lett 184, 1–6 (2002).

    Article  PubMed  CAS  Google Scholar 

  28. 28. K. Mehta, P. Pantazis, T. McQueen, and B. B. Aggarwal, Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs 8, 470–481 (1997).

    Article  PubMed  CAS  Google Scholar 

  29. 29. E. L. White, L. J. Ross, S. M. Schmid, G. J. Kelloff, V. E. Steele, and D. L. Hill, Screening of potential cancer-preventing chemicals for inhibition of induction of ornithine decarboxylase in epithelial cells from rat trachea. Oncol Rep 5, 717–722 (1998).

    PubMed  CAS  Google Scholar 

  30. 30. M. Hasmeda and G. M. Polya, Inhibition of cyclic AMP-dependent protein kinase by curcumin. Phytochemistry 42, 599–605 (1996).

    Article  PubMed  CAS  Google Scholar 

  31. 31. M. T. Huang, T. Lysz, T. Ferraro, T. F. Abidi, J. D. Laskin, and A. H. Conney, Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res 51, 813–819 (1991).

    PubMed  CAS  Google Scholar 

  32. 32. A. Nagao, M. Maeda, B. P. Lim, H. Kobayashi, and J. Terao, Inhibition of beta-carotene-15,15′-dioxygenase activity by dietary flavonoids. J Nutr Biochem 11, 348–355 (2000).

    Article  PubMed  CAS  Google Scholar 

  33. 33. R. L. Hong, W. H. Spohn, and M. C. Hung, Curcumin inhibits tyrosine kinase activity of p185neu and also depletes p185neu. Clin Cancer Res 5, 1884–1891 (1999).

    PubMed  CAS  Google Scholar 

  34. 34. S. C. Gautam, Y. X. Xu, K. R. Pindolia, N. Janakiraman, and R. A. Chapman, Nonselective inhibition of proliferation of transformed and nontransformed cells by the anticancer agent curcumin (diferuloylmethane). Biochem Pharmacol 55, 1333–1337 (1998).

    Article  PubMed  CAS  Google Scholar 

  35. 35. A. Khar, A. M. Ali, B. V. Pardhasaradhi, C. H. Varalakshmi, R. Anjum, and A. L. Kumari, Induction of stress response renders human tumor cell lines resistant to curcumin-mediated apoptosis: role of reactive oxygen intermediates. Cell Stress Chaperones 6, 368–376 (2001).

    Article  PubMed  CAS  Google Scholar 

  36. 36. M. C. Jiang, H. F. Yang-Yen, J. J. Yen, and J. K. Lin, Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer 26, 111–120 (1996).

    Article  PubMed  CAS  Google Scholar 

  37. 37. C. Sun, X. Liu, Y. Chen, and F. Liu, Anticancer effect of curcumin on human B cell non-Hodgkin's lymphoma. J Huazhong Univ Sci Technolog Med Sci 25, 404–407 (2005).

    Article  PubMed  CAS  Google Scholar 

  38. 38. D. Karunagaran, R. Rashmi, and T. R. Kumar, Induction of apoptosis by curcumin and its implications for cancer therapy. Curr Cancer Drug Targets 5, 117–129 (2005).

    Article  PubMed  CAS  Google Scholar 

  39. 39. J. A. Bush, K. J. Cheung, Jr., and G. Li, Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res 271, 305–314 (2001).

    Article  PubMed  CAS  Google Scholar 

  40. 40. L. Moragoda, R. Jaszewski, and A. P. Majumdar, Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res 21, 873–878 (2001).

    PubMed  CAS  Google Scholar 

  41. 41. R. Rashmi, T. R. Santhosh Kumar, and D. Karunagaran, 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 538, 19–24 (2003).

    Article  PubMed  CAS  Google Scholar 

  42. 42. S. Uddin, A. R. Hussain, P. S. Manogaran, K. Al-Hussein, L. C. Platanias, M. I. Gutierrez, and K. G. Bhatia, Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma. Oncogene 24, 7022–7030 (2005).

    Article  PubMed  CAS  Google Scholar 

  43. 43. R. J. Anto, A. Mukhopadhyay, K. Denning, and B. B. Aggarwal, 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 23, 143–150 (2002).

    Article  PubMed  CAS  Google Scholar 

  44. 44. M. L. Kuo, T. S. Huang, and J. K. Lin, Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. Biochim Biophys Acta 1317, 95–100 (1996).

    PubMed  CAS  Google Scholar 

  45. 45. R. Rashmi, S. Kumar, and D. Karunagaran, Ectopic expression of Hsp70 confers resistance and silencing its expression sensitizes human colon cancer cells to curcumin-induced apoptosis. Carcinogenesis 25, 179–187 (2004).

    Article  PubMed  CAS  Google Scholar 

  46. 46. R. Rashmi, S. Kumar, S. and Karunagaran, D. (2004a) Ectopic expression of Bcl-XL or Ku70 protects human colon cancer cells (SW480) against curcumin-induced apoptosis while their down-regulation potentiates it. Carcinogenesis 25, 1867–1877 (2004).

    Article  PubMed  CAS  Google Scholar 

  47. 47. M. Shi, Q. Cai, L. Yao, Y. Mao, Y. Ming, and G. Ouyang, Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int (2006).

    Google Scholar 

  48. 48. G. Radhakrishna Pillai, A. S. Srivastava, T. I. Hassanein, D. P. Chauhan, and E. Carrier, Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett 208, 163–170 (2004).

    Article  PubMed  CAS  Google Scholar 

  49. 49. R. Anjum and A. Khar, Differential regulation of apoptosis in AK-5 tumor cells by the proto-oncogene Bcl-2: presence of Bcl-2 dependent and independent pathways. FEBS Lett 499, 166–170 (2001).

    Article  PubMed  CAS  Google Scholar 

  50. 50. S. Pal, T. Choudhuri, S. Chattopadhyay, A. Bhattacharya, G. K. Datta, T. Das, and G. Sa, Mechanisms of curcumin-induced apoptosis of Ehrlich's ascites carcinoma cells. Biochem Biophys Res Commun 288, 658–665 (2001).

    Article  PubMed  CAS  Google Scholar 

  51. 51. R. Rashmi, S. Kumar, and D. Karunagaran, 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 26, 713–723 (2005).

    Article  PubMed  CAS  Google Scholar 

  52. 52. G. Song, Y. B. Mao, Q. F. Cai, L. M. Yao, G. L. Ouyang, and S. D. Bao, Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression. Braz J Med Biol Res 38, 1791–1798 (2005).

    Article  PubMed  CAS  Google Scholar 

  53. 53. L. D. Zheng, Q. S. Tong, K. X. Tao, L. Wang, and B. Zhang, [Effects of Smac gene overexpression on chemotherapeutic sensitivity of gastric cancer cell line MKN-45]. Ai Zheng 23, 361–366 (2004).

    PubMed  CAS  Google Scholar 

  54. 54. Q. Wang, A. Y. Sun, A. Simonyi, M. D. Jensen, P. B. Shelat, G. E. Rottinghaus, R. S. MacDonald, D. K. Miller, D. E. Lubahn, G. A. Weisman, and G. Y. Sun, Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits. J Neurosci Res 82, 138–148 (2005).

    Article  PubMed  CAS  Google Scholar 

  55. 55. A. Sood, R. Mathew, and H. Trachtman, Cytoprotective effect of curcumin in human proximal tubule epithelial cells exposed to shiga toxin. Biochem Biophys Res Commun 283, 36–41 (2001).

    Article  PubMed  CAS  Google Scholar 

  56. 56. M. Shakibaei, G. Schulze-Tanzil, T. John, and A. Mobasheri, Curcumin protects human chondrocytes from IL-l1beta-induced inhibition of collagen type II and beta1-integrin expression and activation of caspase-3: An immunomorphological study. Ann Anat 187, 487–497 (2005).

    Article  PubMed  CAS  Google Scholar 

  57. 57. S. Fujisawa, T. Atsumi, M. Ishihara, and Y. Kadoma, Cytotoxicity, ROS-generation activity and radical-scavenging activity of curcumin and related compounds. Anticancer Res 24, 563–569 (2004).

    PubMed  CAS  Google Scholar 

  58. 58. A. C. Reddy and B. R. Lokesh, Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Mol Cell Biochem 137, 1–8 (1994).

    Article  PubMed  CAS  Google Scholar 

  59. 59. V. K. Shalini and L. Srinivas, Lipid peroxide induced DNA damage: Protection by turmeric (Curcuma longa). Mol Cell Biochem 77, 3–10 (1987).

    Article  PubMed  CAS  Google Scholar 

  60. 60. M. Subramanian, M. N. Sreejayan, Rao, T. P. Devasagayam, and B. B. Singh, Diminution of singlet oxygen-induced DNA damage by curcumin and related antioxidants. Mutat Res 311, 249–255 (1994).

    PubMed  CAS  Google Scholar 

  61. 61. A. C. Reddyand B. R. Lokesh, Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food Chem Toxicol 32, 279–283 (1994).

    Article  Google Scholar 

  62. 62. E. L. White, L. J. Ross, S. M. Schmid, G. J. Kelloff, V. E. Steele, and D. L. Hill, Screening of potential cancer preventing chemicals for induction of glutathione in rat liver cells. Oncol Rep 5, 507–512 (1998).

    PubMed  CAS  Google Scholar 

  63. 63. H. Ahsan, N. Parveen, N. U. Khan, and S. M. Hadi, Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. Chem Biol Interact 121, 161–175 (1999).

    Article  PubMed  CAS  Google Scholar 

  64. 64. S. Bhaumik, R. Anjum, N. Rangaraj, B. V. Pardhasaradhi, and A. Khar, Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates. FEBS Lett 456, 311–314 (1999).

    Article  PubMed  CAS  Google Scholar 

  65. 65. U. Jacobi, T. Tassopoulos, C. Surber, and J. Lademann, Cutaneous distribution and localization of dyes affected by vehicles all with different lipophilicity. Arch Dermatol Res 297, 303–310 (2006).

    Article  PubMed  CAS  Google Scholar 

  66. 66. A. Paradkar, A. A. Ambike, B. K. Jadhav, and K R. Mahadik,) Characterization of curcumin-PVP solid dispersion obtained by spray drying. Int J Pharm 271, 281–286 (2004).

    Article  PubMed  CAS  Google Scholar 

  67. 67. K. U. Schallreuter and H. Rokos, Turmeric (curcumin): A widely used curry ingredient, can contribute to oxidative stress in Asian patients with acute vitiligo. Indian J Dermatol Venereol Leprol 72, 57–59 (2006).

    Article  PubMed  Google Scholar 

  68. 68. M. Moussavi, K. Assi, A. Gomez-Munoz, and B. Salh, Curcumin mediates ceramide generation via the de novo pathway in colon cancer cells. Carcinogenesis 27, 1636–1644 (2006).

    Article  PubMed  CAS  Google Scholar 

  69. 69. C. Syng-Ai, A. L. Kumari, and A. Khar, Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Mol Cancer Ther 3, 1101–1108 (2004).

    PubMed  CAS  Google Scholar 

  70. 70. S. Somasundaram, N. A. Edmund, D. T. Moore, G. W. Small, Y. Y. Shi, and R. Z. Orlowski, Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 62, 3868–3875 (2002).

    PubMed  CAS  Google Scholar 

  71. 71. M. S. Ahmad, Sheeba, and M Afzal, Amelioration of genotoxic damage by certain phytoproducts in human lymphocyte cultures. Chem Biol Interact 149, 107–115 (2004).

    Article  PubMed  CAS  Google Scholar 

  72. 72. E. Sikora, A. Bielak-Zmijewska, K. Piwocka, J. Skierski, J. and E. Radziszewska, Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment. Biochem Pharmacol 54, 899–907 (1997).

    Article  PubMed  CAS  Google Scholar 

  73. 73. B. B. Aggarwal, Y. Takada, and O. V. Oommen, From chemoprevention to chemotherapy: common targets and common goals. Expert Opin Invest Drugs 13, 1327–1338 (2004).

    Article  CAS  Google Scholar 

  74. 74. C. Jobin, C. A. Bradham, M. P. Russo, B. Juma, A. S. Narula, D. A. Brenner, and R. B. Sartor, Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J Immunol 163, 3474–3483 (1999).

    PubMed  CAS  Google Scholar 

  75. 75. S. Singh and B. B. Aggarwal, Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 270, 24,995–25,000 (1995).

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  77. 77. D. R. Siwak, S. Shishodia, B. B. Aggarwal, and R. Kurzrock, 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 104, 879–890 (2005).

    Article  PubMed  CAS  Google Scholar 

  78. 78. A. Duvoix, F. Morceau, S. Delhalle, M. Schmitz, M. Schnekenburger, M. M. Galteau, M. Dicato, and M. Diederich, Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition. Biochem Pharmacol 66, 1475–1483 (2003).

    Article  PubMed  CAS  Google Scholar 

  79. 79. B. B. Aggarwal, S. Shishodia, Y. Takada, S. Banerjee, R. A. Newman, C. E. Bueso-Ramos, and P. E. Price, 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 11, 7490–7498 (2005).

    Article  PubMed  CAS  Google Scholar 

  80. 80. R. J. Anto, T. T. Maliekal, and D. Karunagaran, L-929 cells harboring ectopically expressed RelA resist curcumin-induced apoptosis. J Biol Chem 275, 15,601–15,604 (2000).

    Article  CAS  Google Scholar 

  81. 81. D. Deeb, H. Jiang, X. Gao, M. S. Hafner, H. Wong, G. Divine, R. A. Chapman, S. A. Dulchavsky, andS. C. Gautam, 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 3, 803–812 (2004).

    PubMed  CAS  Google Scholar 

  82. 82. D. Deeb, Y. X. Xu, H. Jiang, X. Gao, N. Janakiraman, R. A. Chapman, and S. C. Gautam, Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther 2, 95–103 (2003).

    PubMed  CAS  Google Scholar 

  83. 83. S.V. Bava, V. T. Puliappadamba, A. Deepti, A. Nair, D. Karunagaran, and R. J. Anto, 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 280, 6301–6308 (2005).

    Article  PubMed  CAS  Google Scholar 

  84. 84. M. Shi, Q. Cai, L. Yao, Y. Mao, Y. Ming, and G. Ouyang, Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int 30, 221–226 (2006).

    Article  PubMed  CAS  Google Scholar 

  85. 85. W. Henke, K. Ferrell, D. Bech-Otschir, M. Seeger, R. Schade, P. Jungblut, M. Naumann, and W. Dubiel,) Comparison of human COP9 signalsome and 26S proteasome lid'. Mol Biol Rep 26, 29–34 (1999).

    Article  PubMed  CAS  Google Scholar 

  86. 86. J. Rajasingh, H. P. Raikwar, G. Muthian, C. Johnson, and J. J. Bright, 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 340, 359–368 (2006).

    Article  PubMed  CAS  Google Scholar 

  87. 87. A. C. Bharti, N. Donato, and B. B. Aggarwal, Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 171, 3863–3871 (2003).

    PubMed  CAS  Google Scholar 

  88. 88. C. S. Divya and M. R. Pillai, Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol Carcinog 45, 320–332 (2006).

    Article  PubMed  CAS  Google Scholar 

  89. 89. M. Tomita, H. Kawakami, J. N. Uchihara, T. Okudaira, M. Masuda, N. Takasu, T. Matsuda, T. Ohta, Y. Tanaka, and N. Mori, Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines. Leuk Res 30, 313–321 (2006).

    Article  PubMed  CAS  Google Scholar 

  90. 90. C. Bernt, T. Vennegeerts, U. Beuers, and C. Rust, The human transcription factor AP-1 is a mediator of bile acid-induced liver cell apoptosis. Biochem Biophys Res Commun 340, 800–806 (2006).

    Article  PubMed  CAS  Google Scholar 

  91. 91. Y. R. Chen and T. H. Tan, Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene 17, 173–178 (1998).

    Article  PubMed  CAS  Google Scholar 

  92. 92. A. R. Hussain, M. Al-Rasheed, P. S. Manogaran, K. A. Al-Hussein, L. C. Platanias, K. A. Kuraya, and S. Uddin, Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in Acute T cell Leukemias. Apoptosis 11, 245–254 (2006).

    Article  PubMed  CAS  Google Scholar 

  93. 93. L. R. Chaudhary and K. A. Hruska, Inhibition of cell survival signal protein kinase B/Akt by curcumin in human prostate cancer cells. J Cell Biochem 89, 1–5 (2003).

    Article  PubMed  CAS  Google Scholar 

  94. 94. L. Korutla and P. Kumar, Inhibitory effect of curcumin on epidermal growth factor receptor kinase activity in A431 cells. Biochim Biophys Acta 1224, 597–600 (1994).

    Article  PubMed  Google Scholar 

  95. 95. A. Chen, J. Xu, and A. C. Johnson, Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 25, 278–287 (2006).

    PubMed  Google Scholar 

  96. 96. D. W. Scott and G. Loo, Curcumin-induced GADD153 gene up-regulation in human colon cancer cells. Carcinogenesis 25, 2155–2164 (2004).

    Article  PubMed  CAS  Google Scholar 

  97. 97. G P. Collett and F. C. Campbell, Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells. Carcinogenesis 25, 2183–2189 (2004).

    Article  PubMed  CAS  Google Scholar 

  98. 98. S. Zheng and A. Chen, Activation of PPARgamma is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro. Biochem J 384, 149–157 (2004).

    Article  PubMed  CAS  Google Scholar 

  99. 99. S. Zheng and A. Chen, Curcumin suppresses the expression of extracellular matrix genes in activated hepatic stellate cells by inhibiting gene expression of connective tissue growth factor. Am J Physiol Gastrointest Liver Physiol 290, G883–893 (2005).

    Article  PubMed  Google Scholar 

  100. 100. L. Zheng, Q. Tong, and C. Wu, Growth-inhibitory effects of curcumin on ovary cancer cells and its mechanisms. J Huazhong Univ Sci Technolog Med Sci 24, 55–58 (2004).

    Article  PubMed  CAS  Google Scholar 

  101. 101. S. Sen, H. Sharma, and N. Singh, Curcumin enhances Vinorelbine mediated apoptosis in NSCLC cells by the mitochondrial pathway. Biochem Biophys Res Commun 331, 1245–1252 (2005).

    Article  PubMed  CAS  Google Scholar 

  102. 102. T. C. Hour, J. Chen, C. Y. Huang, J. Y. Guan, S. H. Lu, and Y. S. Pu, Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation. Prostate 51, 211–218 (2002).

    Article  PubMed  CAS  Google Scholar 

  103. 103. M. M. Chan, D. Fong, K. J. Soprano, W. F. Holmes, and H. Heverling, Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J Cell Physiol 194, 63–70 (2003).

    Article  PubMed  CAS  Google Scholar 

  104. 104. J. Y. Koo, H. J. Kim, K. O. Jung, and K. Y. Park, Curcumin inhibits the growth of AGS human gastric carcinoma cells in vitro and shows synergism with 5-fluorouracil. J Med Food 7, 117–121 (2004).

    Article  PubMed  CAS  Google Scholar 

  105. 105. B. Du, L. Jiang, Q. Xia, and L. Zhong, Synergistic inhibitory effects of curcumin and 5-fluorouracil on the growth of the human colon cancer cell line HT-29. Chemotherapy 52, 23–28 (2006).

    Article  PubMed  CAS  Google Scholar 

  106. 106. P. Limtrakul, S. Anuchapreeda, and D. Buddhasukh, Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids. BMC Cancer 4, 13 (2004).

    Article  PubMed  Google Scholar 

  107. 107. S. E. Chuang, P. Y. Yeh, Y. S. Lu, G. M. Lai, C. M. Liao, M. Gao, and A. L. Cheng, Basal levels and patterns of anticancer drug-induced activation of nuclear factor-kappaB (NF-kappaB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells. Biochem Pharmacol 63, 1709–1716 (2002).

    Article  PubMed  CAS  Google Scholar 

  108. 108. S. Lev-Ari, L. Strier, D. Kazanov, O. Elkayam, D. Lichtenberg, D. Caspi, and N. Arber, Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells. Rheumatology (Oxford) 45, 171–177 (2006).

    Article  CAS  Google Scholar 

  109. 109. T. O. Khor, Y. S. Keum, W. Lin, J. H. Kim, R. Hu, G. Shen, C. Xu, A. Gopalakrishnan, B. Reddy, X. Zheng, A. H. Conney, and A. N. Kong, Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res 66, 613–621 (2006).

    Article  PubMed  CAS  Google Scholar 

  110. 110. J. H. Kim, C. Xu, Y. S. Keum, B. Reddy, A. Conney, and A. N. Kong, Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with β-phenylethyl isothiocyanate and curcumin. Carcinogenesis 27, 475–482 (2006).

    Article  PubMed  CAS  Google Scholar 

  111. 111. A. Spingarn, P. G. Sacks, D. Kelley, A. J. Dannenberg, and S. P. Schantz,) Synergistic effects of 13-cis retinoic acid and arachidonic acid cascade inhibitors on growth of head and neck squamous cell carcinoma in vitro. Otolaryngol Head Neck Surg 118, 159–164 (1998).

    Article  PubMed  CAS  Google Scholar 

  112. 112. Y. Liu, R. L. Chang, X. X. Cui, H. L. Newmark, and A. H. Conney, Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells. Oncol Res 9, 19–29 (1997).

    PubMed  CAS  Google Scholar 

  113. 113. D. Chendil, R. S. Ranga, D. Meigooni, S. Sathishkumar, and M. M. Ahmed, Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene 23, 1599–1607 (2004).

    Article  PubMed  CAS  Google Scholar 

  114. 114. C. Ramachandran, S. Rodriguez, R. Ramachandran, P. K. Raveendran Nair, H. Fonseca, Z. Khatib, E. Escalon, and S. J. Melnick, Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res 25, 3293–3302 (2005).

    PubMed  CAS  Google Scholar 

  115. 115. B. K. Adams, J. Cai, J. Armstrong, M. Herold, Y. J. Lu, A. Sun, J. P. Snyder, D. C. Liotta, D.P. Jones, and M. Shoji, EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs 16, 263–275 (2005).

    Article  PubMed  CAS  Google Scholar 

  116. 116. M. S. Furness, T. P. Robinson, T. Ehlers, R. B. T. Hubbard, J. L. Arbiser, D. J. Goldsmith, and J. P. Bowen, Antiangiogenic agents: Studies on fumagillin and curcumin analogs. Curr Pharm Des 11, 357–373 (2005).

    Article  PubMed  CAS  Google Scholar 

  117. 117. Q. S. Tong, L. D. Zheng, P. Lu, F. C. Jiang, F. M. Chen, F. Q. Zeng, L. Wang, and J. H. Dong, Apoptosis-inducing effects of curcumin derivatives in human bladder cancer cells. Anticancer Drugs 17, 279–287 (2006).

    Article  PubMed  CAS  Google Scholar 

  118. 118. W. M. Weber, L. A. Hunsaker, S. F. Abcouwer, L. M. Deck, and D. L.Vander Jagt, Anti-oxidant activities of curcumin and related enones. Bioorg Med Chem 13, 3811–3820 (2005).

    Article  PubMed  CAS  Google Scholar 

  119. 119. K. M. Youssef and M. A. El-Sherbeny, Synthesis and antitumor activity of some curcumin analogs. Arch Pharm (Weinheim) 338, 181–189 (2005).

    Article  CAS  Google Scholar 

Download references

Authors
  1. Devarajan Karunagaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeena Joseph
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thankayyan R. Santhosh Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Ransom Horne, Jr., Professor of Cancer Research Professor of Cancer Medicine (Biochemistry)and Chief, Cytokine Research Section Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston,, TX, 143, 77030, USA

    Bharat B. Aggarwal Ph.D.

  2. Chief and Professor National Research Laboratory of Molecular Carcinogenesis and Chemoprevention College of Pharmacy, Seoul National University, Shillim-dong, Kwanak-gu, Seoul, 151-742, South Korea

    Young-Joon Surh Ph.D.

  3. Assistant Professor Department of Biology, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA

    Shishir Shishodia Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer

About this chapter

Cite this chapter

Karunagaran, D., Joseph, J., Santhosh Kumar, T.R. (2007). CELL GROWTH REGULATION. In: Aggarwal, B.B., Surh, YJ., Shishodia, S. (eds) The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY, vol 595. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-46401-5_11

Download citation

Publish with us

Policies and ethics

Search

Navigation