Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB.
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.
Kim
Sun Mi
SM
College of Pharmacy, Chungbuk National University, 48, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
Lee
So Yong
SY
Cho
Jin Suk
JS
Son
Seung Mo
SM
Choi
Sang Sook
SS
Yun
Yeo Pyo
YP
Yoo
Hwan Soo
HS
Yoon
Do Young
DY
Oh
Ki-Wan
KW
Han
Sang Bae
SB
Hong
Jin Tae
JT
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
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