title: Growth inhibition and apoptosis induced by lupeol, a dietary triterpene, in human hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) is the fifth most malignant tumor worldwide and is known to be resistant to conventional chemotherapy. New therapeutic strategies are urgently needed for treating HCC. Lup-20(29)-en-3H-ol (Lupeol), a novel dietary triterpene, is found in fruits, vegetables, and medicinal plants and possesses multiple bio-activities with very low toxicity. In the current study, we investigated its growth-inhibitory effects in HCC cell lines SMMC7721 and HepG2. In the in vitro studies, lupeol treatment alone caused decrease of cell viability in two HCC cell lines in a dose-dependent manner. It also induced apoptosis and caused cell accumulation in S phase. Further analysis revealed the induction of active caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage by lupeol treatment. In the in vivo studies, nude mice implanted with SMMC7721 cells subcutaneously were treated with lupeol three times a week and tumor development was significantly inhibited. We further investigated the combination anti-tumor effect of lupeol and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in HCC, considering TRAIL treatment alone could not achieve high level of anti-tumor effect. The results demonstrated that lupeol could exert a combinational effect with TRAIL, resulting in chemosensitization of HCC. Our results suggested that lupeol alone or as an adjuvant to therapeutic agents could be developed as a potential agent for treating HCC.
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Institute of Biology and Medical Sciences, Soochow University, Suzhou, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Lurong
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yunsen
authors.initials: Y
authors.lastname: Li
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D053978:Pentacyclic Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology / Q000627:therapeutic use; D000094042:Lupanes
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D011065:Poly(ADP-ribose) Polymerases; D053221:TNF-Related Apoptosis-Inducing Ligand; C010480:lupeol; D000094042:Lupanes