title: Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB.
abstract: Ginsenoside Rg3 has been a subject of interest for use as a cancer preventive or therapeutic agent. Nuclear factor-kappa (NF-kappaB) is constitutively activated in prostate cancer, and gives cancer cells resistance to chemotherapeutic agents. To investigate whether Rg3 can suppress the activation of NF-kappaB, and thus increase susceptibility of prostate (LNCaP and PC-3, DU145) cells against chemotherapeutics, prostate cancer cell growth as well as activation of NF-kappaB was examined. We found that a combination treatment of Rg3 (50 microM) with a conventional agent docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis as well as G(0)/G(1) arrest accompanied with the significant inhibition of NF-kappaB activity than those by treatment of Rg3 or docetaxel alone. It was also found that NF-kappaB target gene expression of Bax, caspase-3, and caspase-9 was much more significantly enhanced, but the expression of Bcl-2, inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP), and the expression of cell cycle regulatory proteins cyclin B, D1 and E, and cyclin dependent kinases 2 and 4 was also much more significantly inhibited by the combination treatment. The combination of Rg3 (50 microM) with cisplatin (10 microM) and doxorubicin (2 microM) was also more effective in the inhibition of prostate cancer cell growth and NF-kappaB activity than those by the treatment of Rg3 or chemotherapeutics alone. These results indicate that ginsenoside Rg3 inhibits NF-kappaB, and enhances the susceptibility of prostate cancer cells to docetaxel and other chemotherapeutics. Thus, ginsenoside Rg3 could be useful as an anti-cancer agent.
authors.affiliation: College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: So Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Jin Suk
authors.initials: JS
authors.lastname: Cho
authors.forename: Seung Mo
authors.initials: SM
authors.lastname: Son
authors.forename: Sang Sook
authors.initials: SS
authors.lastname: Choi
authors.forename: Yeo Pyo
authors.initials: YP
authors.lastname: Yun
authors.forename: Hwan Soo
authors.initials: HS
authors.lastname: Yoo
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000302:isolation & purification / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D036145:Ginsenosides; D016328:NF-kappa B; D043823:Taxoids; D000077143:Docetaxel; C097367:ginsenoside Rg3; D004317:Doxorubicin; D002945:Cisplatin