Lupeol, a dietary triterpene, inhibited growth, and induced apoptosis through down-regulation of DR3 in SMMC7721 cells.
Lupeol (Lup-20(29)-en-3H-ol), a novel dietary triterpene, was found in fruits, vegetables, and several medicinal plants. Here, we investigated its growth-inhibitory effect and associated mechanisms in hepatocellular carcinoma SMMC7721 cells. Lupeol treatment resulted in significant inhibition of cell viability in a dose-dependent manner and caused apoptotic death of this cell line with activation of caspase3 expression. Caspase8 inhibitor pretreatment was found to partially block the apoptosis induced by Lupeol. Moreover, Lupeol specifically caused a significant decrease in the expression of Death receptor 3 (DR3) mRNA and protein and a significant elevated expression of FADD mRNA whereas Fas mRNA and protein expression was not detectable. Further more, knockdown of DR3 by small interfering RNA inhibited the growth and induced apoptosis of hepatocellular carcinoma cell. These results suggested that Lupeol treatment induced growth inhibition and apoptosis in SMMC7721 cells, the mechanism is due to down-regulation of DR3 expression. We demonstrated that Lupeol appears to be a promising chemopreventive agent for treating hepatocellular carcinoma, and DR3 may be an important target for liver cancer therapy.
Zhang
Lin
L
Department of Surgery, Lanzhou University Second Hospital, Gansu Province, China.
Zhang
Youcheng
Y
Zhang
Lingyi
L
Yang
Xiaojun
X
Lv
Zhicheng
Z
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D053181:Caspase 8 / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053200:Fas-Associated Death Domain Protein / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger / Q000032:analysis; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D000094042:Lupanes
D053148:Caspase 3; D053181:Caspase 8; D053200:Fas-Associated Death Domain Protein; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger; D053219:Receptors, Tumor Necrosis Factor, Member 25; D014315:Triterpenes; C505533:FADD protein, human; C506033:TNFRSF25 protein, human; C010480:lupeol; D000094042:Lupanes