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: Yan He, Fen Liu, Lurong Zhang, Yan Wu, Bo Hu, Yinsheng Zhang, Yunsen Li, Haiyan Liu
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 34 Issue 4 Pg. 517-22 ( 2011) ISSN: 1347-5215 [Electronic] Japan
• PMID: 21467639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Pentacyclic Triterpenes
• Plant Extracts
• TNF-Related Apoptosis-Inducing Ligand
• Poly(ADP-ribose) Polymerases
• Caspase 3
• lupeol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (metabolism, prevention & control)
• Caspase 3 (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chemotherapy, Adjuvant
• Dose-Response Relationship, Drug
• Hep G2 Cells
• Humans
• Liver Neoplasms (metabolism, prevention & control)
• Mice
• Mice, Nude
• Pentacyclic Triterpenes (pharmacology, therapeutic use)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Poly(ADP-ribose) Polymerases (metabolism)
• TNF-Related Apoptosis-Inducing Ligand (pharmacology, therapeutic use)