title: Matrine-induced autophagy regulated by p53 through AMP-activated protein kinase in human hepatoma cells.
abstract: Matrine, one of the main extract components of Sophora flavescens, has been shown to exhibit inhibitory effects on some tumors through autophagy. However, the mechanism underlying the effect of matrine remains unclear. The cultured human hepatocellular carcinoma cell line HepG2 and SMMC‑7721 were treated with matrine. Signal transduction and gene expression profile were determined. Matrine stimulated autophagy in SMMC‑7721 cells in a mammalian target of rapamycin (mTOR)-dependent manner, but in an mTOR-independent manner in HepG2 cells. Next, in HepG2 cells, autophagy induced by matrine was regulated by p53 inactivation through AMP-activated protein kinase (AMPK) signaling transduction, then AMPK suppression switched autophagy to apoptosis. Furthermore, the interferon (IFN)-inducible genes, including interferon α-inducible protein 27 (IFI27) and interferon induced transmembrane protein 1 (IFITM1), which are downstream effector of p53, might be modulated by matrine-induced autophagy. In addition, we found that the p53 protein isoforms, p53β, p53γ, ∆133p53, and ∆133p53γ, due to alternative splicing of intron 9, might be regulated by the p53-mediated autophagy. These results show that matrine induces autophagy in human hepatoma cells through a novel mechanism, which is p53/AMPK signaling pathway involvement in matrine-promoted autophagy.
authors.affiliation: The Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Shan-Bu
authors.initials: SB
authors.lastname: Xie
authors.affiliation: The Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China.
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: He
authors.affiliation: The Department of Gastroenterology, China-Japan Friendship Hospital, Ministry of Health, Beijing 100029, P.R. China.
authors.forename: Shu-Kun
authors.initials: SK
authors.lastname: Yao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D011807:Quinolizines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D055372:AMP-Activated Protein Kinases; D000093842:Matrines