Abstract
Ginseng has an anti-cancer effect in several cancer models. This study was to characterize active constituents of ginseng and their effects on proliferation of prostate cancer cell lines, LNCaP and PC3. Cell proliferation was measured by [3H]thymidine incorporation, the intracellular calcium concentration by a dual-wavelength spectrophotometer system, effects on mito-gen-activated protein (MAP) kinases by Western blotting, and cell attachment and morphologic changes were observed under a microscope. Among 11 ginsenosides tested, ginsenosides Rg3 and Rh2 inhibited the proliferation of prostate cancer cells. EC50s of Rg3 and Rh2 on PC3 cells were 8.4 μM and 5.5 μM, respectively, and 14.1 μM and 4.4 μM on LNCaP cells, respectively. Both ginsenosides induced cell detachment and modulated three modules of MAP kinases activities differently in LNCaP and PC3 cells. These results suggest that ginsenosides Rg3 and Rh2-induced cell detachment and inhibition of the proliferation of prostate cancer cells may be associated with modulation of three modules of MAP kinases.
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Bai, C. X., Sunami, A., Namiki, T., Sawanobori, T., and Furukawa, T., Electrophysiological effects of ginseng and ginsenoside Re in guinea pig ventricular myocytes.Eur. J. Pharmacol., 476, 35–44 (2003).
Chang, L. and Karin, M., Mammalian MAP kinase signalling cascades.Nature, 410, 37–40 (2001).
Choi, S., Jung, S. Y., Ko, Y. S., Koh, S. R., Rhim, H., and Nah, S. Y., Functional expression of a novel ginsenoside Rf binding protein from rat brain mRNA in Xenopus laevis oocytes.Mol. Pharmacol., 61, 928–935 (2002).
Fei, X. F., Wang, B. X., Tashiro, S., Li, T. J., Ma, J. S., and Ikejima, T., Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells.Acta Pharmacol. Sin., 23, 315–322 (2002).
Hommes, D. W., Peppelenbosch, M. P., and van Deventer, S. J., Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets.Gut, 52, 144–151 (2003).
Hooks, S. B., Santos, W. L., Im, D. S., Heise, C. E., Macdonald, T. L., and Lynch, K. R., Lysophosphatidic acid-induced mitogenesis is regulated by lipid phosphate phosphatases and is Edg-receptor independent.J. Biol. Chem., 276, 4611–4621 (2001).
Im, D. S., Heise, C. E., Harding, M. A., George, S. R., O’Dowd, B. F., Theodorescu, D., and Lynch, K. R., Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate.Mol. Pharmacol., 57, 753–759 (2000).
Kim, N. D., Kang, S. Y., Kim, M. J., Park, J. H., and Schini-Kerth, V. B., The ginsenoside Rg3 evokes endothelium-independent relaxation in rat aortic rings: role of K+ channels.Eur. J. Pharmacol., 367, 51–57 (1999).
Kim, N. D., Kang, S. Y., Park, J. H., and Schini-Kerth, V. B., Ginsenoside Rg3 mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of K+ channels.Eur. J. Pharmacol., 367, 41–49 (1999).
Kim, Y. S., Kim, D. S., and Kim, S. I., Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytes: modulation of protein kinase C isoforms during differentiation by ginsenoside Rh2.Int. J. Biochem. Cell Biol., 30, 327–338 (1998).
Kim, Y. S., Jin, S. H., Lee, Y. H., Park, J. D., and Kim, S. I., Differential expression of protein kinase C subtypes during ginsenoside Rh2-lnduced apoptosis in SK-N-BE(2) and C6Bu-1 cells.Arch. Pharm. Res., 23, 518–524 (2000).
Lee, S. R., Park, J. H., Choi, K. J., and Kim, N. D., Inhibitory effects of ginsenoside Rg3 on platelet aggregation and its mechanism of action.Kor. J. Ginseng Sci., 21, 132–140 (1997).
Lee, Y. N., Lee, H. Y., Chung, H. Y., Kim, S. I., Lee, S. K., Park, B. C., and Kim, K. W.,In vitro induction of differentiation by ginsenoides in F9 teratocarcinoma cells.Eur. J. Cancer, 32A, 1420–1428 (1996).
Liao, B., Newmark, H., and Zhou, R., Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neuronsin vitro.Exp. Neurol., 173, 224–234 (2002).
Liu, W. K., Xu, S. X., and Che, C. T., Anti-proliferative effect of ginseng saponins on human prostate cancer cell line.Life Sci., 67, 1297–1306 (2000).
Nah, S. Y., Park, H. J., and McCleskey, E. W., A trace component of ginseng that inhibits Ca2+ channels through a pertussis toxin-sensitive G protein.Proc. Natl. Acad. Sci. U. S. A., 92, 8739–8743 (1995).
Nakata, H., Kikuchi, Y., Tode, T., Hirata, J., Kita, T., Ishii, K., Kudoh, K., Nagata, I., and Shinomiya, N., Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells.Jpn. J. Cancer Res., 89, 733–740 (1998).
Odashima, S., Ohta, T., Kohno, H., Matsuda, T., Kitagawa, I., Abe, H., and Arichi, S., Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides.Cancer Res., 45, 2781–2784 (1985).
Oh, M., Choi, Y. H., Choi, S., Chung, H., Kim, K., Kim, S. I., Kim, D. K., and Kim, N. D., Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells.Int. J. Oncol., 14, 869–875 (1999).
Ohta, H., Sato, K., Murata, N., Damirin, A., Malchinkhuu, E., Kon, J., Kimura, T., Tobo, M., Yamazaki, Y., Watanabe, T., Yagi, M., Sato, M., Suzuki, R., Murooka, H., Sakai, T., Nishitoba, T., Im, D. S., Nochi, H., Tamoto, K., Tomura, H., and Okajima, F., KM6425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors.Mol. Phanvacol., 64, 994–1005 (2003).
Park, J. A., Lee, K. Y., Oh, Y. J., Kim, K. W., and Lee, S. K., Activation of caspase-3 protease via a Bcl-2-insensitive pathway during the process of ginsenoside Rh2-induced apoptosis.Cancer Lett., 121, 73–81 (1997).
Putney, J. W., {jrJr.} and Bird, G. S., The inositol phosphate-calcium signaling system in nonexcitable cells.Endocr. Rev., 14, 610–631 (1993).
Rhim, H., Kim, H., Lee, D. Y., Oh, T. H., and Nah, S. Y., Ginseng and ginsenoside Rg3, a newly identified active ingredient of ginseng, modulate Ca2+ channel currents in rat sensory neurons.Eur. J. Pharmacol., 436, 151–158 (2002).
Rhim, J. S. and Kung, H. F., Human prostate carcinogenesis.Crit. Rev. Oncog., 8, 305–328 (1997).
Sandler, H. M., Narayan, S., and Smith, D. C., Combined modality treatment for prostate cancer: role of chemotherapy.Semin. Oncol., 30, 95–100 (2003).
See, W. A., Adjuvant hormone therapy after radiation or surgery for localized or locally advanced prostate cancer.Curr. Treat. Options Oncol., 4, 351–362 (2003).
Teicher, B. A., Kakeji, Y., Ara, G., Herbst, R. S., and Northey, D., Prostate carcinoma response to cytotoxic therapy: in vivo resistance.In Vivo, 11, 453–461 (1997).
Theyer, G., Schirmbock, M., Thalhammer, T., Sherwood, E. R., Baumgartner, G., and Hamilton, G., Role of the MDR-1- encoded multiple drug resistance phenotype in prostate cancer cell lines.J. Urol., 150, 1544–1547 (1993).
Wasilenko, W. J., Cooper, J., Palad, A. J., Somers, K. D., Blackmore, P. F., Rhim, J. S., Wright, G. L., {jrJr.}, and Schellhammer, P. F., Calcium signaling in prostate cancer cells: evidence for multiple receptors and enhanced sensitivity to bombesin/GRP.Prostate, 30, 167–173 (1997).
Yun, T. K., Lee, Y. S., Lee, Y. H., Kim, S. I., and Yun, H. Y., Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds.J. Kor. Med. Sci., 16 Suppl, S6–18(2001).
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Kim, HS., Lee, EH., Ko, SR. et al. Effects of ginsenosides Rg3 and Rh2 on the proliferation of prostate cancer cells. Arch Pharm Res 27, 429–435 (2004). https://doi.org/10.1007/BF02980085
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DOI: https://doi.org/10.1007/BF02980085