Ginsenoside Rh2 induces Bcl-2 family proteins-mediated apoptosis in vitro and in xenografts in vivo models

Journal of Cellular Biochemistry

Volumn 112, Issue 1, 2011, Pages 330-340

  Choi, Sunga ^a   Oh, Jun Young ^b   Kim, Soo Jin ^b  

^a Chungnam National University   (South Korea)

^b Hallym University   (South Korea)

Author keywords

Apoptosis; Bcl 2 family proteins; Breast cancer; Ginsenoside RH2; Xenograft

Indexed keywords

BIM PROTEIN; GINSENOSIDE RH 2; PROTEIN BAK; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; SMALL INTERFERING RNA;

ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL STRAIN MCF 7; CONTROLLED STUDY; DRUG EFFECT; FEMALE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR DOWN REGULATION; XENOGRAFT;

ANIMALS; APOPTOSIS; CELL LINE, TUMOR; DOWN-REGULATION; FEMALE; GINSENOSIDES; HUMANS; MICE; MICE, NUDE; PROTO-ONCOGENE PROTEINS C-BCL-2; TRANSPLANTATION, HETEROLOGOUS;

MUS; PANAX GINSENG;

EID: 78651342562     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.22932     Document Type: Article

References (42)

1. Abe H, Arichi S, Hayashi T, Odashima S. 1979. Ultrastructural studies of Morris hepatoma cells reversely transformed by ginsenosides. Experientia 35:1647-1649. (Pubitemid 10099151)
2. Adams JM, Cory S. 1998. The Bcl-2 protein family: Arbiters of cell survival. Science 281:1322-1326.
3. Chao DT, Korsmeyer SJ. 1998. Bcl-2 family: Regulators of cell death. Annu Rev Immunol 16:395-419.
4. Cheng CC, Yang SM, Huang CY, Chen JC, Chang WM, Hsu SL. 2005. Molecular mechanisms of ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells. Cancer Chemother Pharmacol 55:531-540.
5. Choi S, Kim TW, Singh SV. 2009. Ginsenoside Rh2-mediated G1 phase cell cycle arrest in human breast cancer cells is caused by p15Ink4B and p27Kip1-dependent Inhibition of cyclin-dependent kinases. Pharm Res 26:2280-2288.
6. Cohen JH, Kristal AR, Stanford JL. 2000. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 92:61-68.
7. Cuzick J, Forbes J, Edwards R, Baum M, Cawthorn S, Coates A, Hamed A, Howell A, Powles T, IBIS Investigators. 2002. First results from the International Breast Cancer Intervention study (IBIS-I): A randomized prevention trial. Lancet 360:817-824.
8. Du C, Fang M, Li Y, Li L, Wang X. 2000. Smac, a mitochondrial protein that promotes cytochrome c dependent caspase activation by eliminating IAP inhibition. Cell 102:33-42.
9. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N. 1998. Tamoxifen for prevention of breast cancer: Report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90:1371-1388.
10. Green DR, Reed JC. 1998. Mitochondria and apoptosis. Science 281:1309-1312.
11. Ham YM, Lim JH, Na HK, Choi JS, Park BD, Yim H, Lee SK. 2006. Ginsenoside-Rh2-induced mitochondrial depolarization and apoptosis are associated with reactive oxygen species- and Ca2+-mediated c-Jun NH2-terminal kinase 1 activation in HeLa cells. J Pharmacol Exp Ther 319:1276-1285.
12. Hengartner MO. 2000. The biochemistry of apoptosis. Nature 407:770-776.
13. Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ. 1990. Bcl- 2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334-336.
14. Huang J, Tang XH, Ikejima T, Sun XJ, Wang XB, Xi RG, Wu LJ. 2008. A new triterpenoid from Panax ginseng exhibits cytotoxicity through p53 and the caspase signaling pathway in the HepG2 cell line. Arch Pharm Res 31:323-329.
15. Hulka BS, Stark AT. 1995. Breast cancer: Cause and prevention. Lancet 346:883-887.
16. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. 2006. Cancer statistics. CA Cancer J Clin 56:106-130.
17. Jia WW, Bu X, Philips D, Yan H, Liu G, Chen X, Bush JA, Li G. 2004. Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy. Can J Physiol Pharmacol 82:431-437.
18. Kelsey JL, Bernstein L. 1996. Epidemiology and prevention of breast cancer. Annu Rev Pubic Health 17:47-67.
19. Kelsey JL, Gammon MD, John EM. 1993. Reproductive factors and breast cancer. Epidemiol Rev 15:36-47.
20. Kim YS, Jin SH. 2004. Ginsenoside Rh2 induces apoptosis via activation of caspase-1 and -3 and up-regulation of Bax in human neuroblastoma. Arch Pharm Res 27:834-839.
21. Kim YS, Jin SH, Lee YH, Kim SI, Park JD. 1999. Ginsenoside Rh2 induces apoptosis independently of Bcl-2, Bcl-xL, or Bax in C6Bu-1 cells. Arch Pharm Res 22:448-453.
22. Kim HS, Lee EH, Ko SR, Choi KJ, Park JH, Im DS. 2004. Effects of ginsenosides Rg3 and Rh2 on the proliferation of prostate cancer cells. Arch Pharm Res 27:429-435.
23. Kim SY, Kim DH, Han SJ, Hyun JW, Kim HS. 2007. Repression of matrix metalloproteinase gene expression by ginsenoside Rh2 in human astroglioma cells. Biochem Pharmacol 74:1642-1651.
24. Kitts DD, Popovich DG, Hu C. 2007. Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured leukemia (THP-1) cells. Can J Physiol Pharmacol 85:1173-1183.
25. Lee KY, Park JA, Chung E, Lee YH, Kim SI, Lee SK. 1996. Ginsenoside-Rh2 blocks the cell cycle of SK-HEP-1 cells at the G1/S boundary by selectively inducing the protein expression of p27kip1. Cancer Lett 110:193-200.
26. Liu X, Kim C, Yang J, Jemmerson R, Wang X. 1996. Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c. Cell 86:147-157.
27. Musende AG, Eberding A, Wood C, Adomat H, Fazli L, Hurtado-Coll A, Jia W, Bally MB, Guns ET. 2009. Pre-clinical evaluation of Rh2 in PC-3 human xenograft model for prostate cancer in vivo: Formulation, pharmacokinetics, biodistribution and efficacy. Cancer Chemother Pharmacol 64:1085-1095.
28. Nakata H, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, Kudoh K, Nagata I, Shinomiya N. 1998. Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells. Jpn J Cancer Res 89:733-740.
29. Odashima S, Ohta T, Kohno H, Matsuda T, Kitagawa I, Abe H, Arichi S. 1985. Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides. Cancer Res 45:2781-2784.
30. Oh M, Choi YH, Choi SH, Chung H, Kim K, Kim SI, Kim DK, Kim ND. 1999. Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int J Oncol 14:869-875.
31. Park JA, Lee KY, Oh YJ, Kim KW, Lee SK. 1997. Activation of caspase-3 protease via a Bcl-2-insensitive pathway during the process of ginsenoside Rh2-induced apoptosis. Cancer Lett 121:73-81.
32. Reed JC. 1997. Bcl-2 family proteins: Regulators of apoptosis and chemoresistance in hematologic malignancies. Semin Hematol 34:9-19.
33. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G. 1999. Molecular characterization of mitochondrial apoptosis-inducing factors. Nature 397: 441-446.
34. Terry G, Ho L, Londesborough P, Duggan C, Hanby A, Cuzick J. 2007. The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions. Br J Cancer 96:110-117.
35. Thornberry N, Lazebnick Y. 1998. Caspases: Enemies within. Science 281: 1312-1316.
36. Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA. 1996. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev 57:33-48.
37. Wang Z, Zheng Q, Liu K, Li G, Zheng R. 2006. Ginsenoside Rh2 enhances antitumor activity and decreases genotoxic effect of cyclophosphamide. Basic Clin Pharmacol Toxicol 98:411-415.
38. Wolf BB, Green DR. 1999. Suicidal tendencies: Apoptotic cell death by caspase family proteinases. J Biol Chem 274:20049-20052.
39. Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ. 1997. Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol 139:1281-1292.
40. Xie X, Eberding A, Madera C, Fazli L, Jia W, Goldenberg L, Gleave M, Guns ES. 2006. Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer models. J Urol 175:1926-1931.
41. Yamaguchi H, Wang HG. 2001. The protein kinase PKB/Akt regulates cell survival and apoptosis by inhibiting Bax conformational change. Oncogene 20:7779-7786.
42. Yun TK, Meyer CA. 2001. Brief introduction of Panax ginseng. J Korean Med Sci 16:S3.