title: Potentiation of resveratrol-induced apoptosis by matrine in human hepatoma HepG2 cells.
abstract: Resveratrol, a natural polyphenolic phytochemical, has received considerable attention due to its potential chemopreventive and chemotherapeutic properties. In the present study, we first evaluated the growth-inhibitory effect of resveratrol on HepG2 cells and explored the underlying molecular mechanisms. Resveratrol inhibited proliferation and induced apoptosis in HepG2 cells via activation of caspase-9 and caspase-3, upregulation of the Bax/Bcl-2 ratio and induction of p53 expression. Cell cycle analysis demonstrated that resveratrol arrested cell cycle progression in the G1 and S phase. We further focused on the combination of matrine, a natural component extracted from the traditional Chinese medical herb Sophora flavescens Ait., as a mechanism to potentiate the growth-inhibitory effect of resveratrol on HepG2 cells. Both MTT and colony formation assay results indicated that the combined treatment of resveratrol and matrine exhibited a synergistic antiproliferative effect. In addition, resveratrol-induced apoptosis was significantly enhanced by matrine, which could be attributed to activation of caspase-3 and caspase-9, downregulation of survivin, induction of reactive oxygen species (ROS) generation and disruption of mitochondria membrane potential (Δψm). Our findings suggest that the combination treatment of resveratrol and matrine is a promising novel anticancer strategy for liver cancer; it also provides new insights into the mechanisms of combined therapy.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China.
authors.forename: Xiuyuan
authors.initials: X
authors.lastname: Ou
authors.affiliation: Academy of the State Administration of Grain, Beijing 100037, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China.
authors.forename: Xumeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China.
authors.forename: Qiyang
authors.initials: Q
authors.lastname: He
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053148:Caspase 3 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011807:Quinolizines / Q000008:administration & dosage*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D000093842:Matrines
chemical_list: D000470:Alkaloids; D019253:Proto-Oncogene Proteins c-bcl-2; D011807:Quinolizines; D013267:Stilbenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9; D000077185:Resveratrol; D000093842:Matrines