title: EHHM, a novel phenolic natural product fromLivistona chinensis, induces autophagy-related apoptosis in hepatocellular carcinoma cells.
abstract: Hepatocellular carcinoma (HCC) ranks the second cause of cancer-associated mortality worldwide. In the present study, the effects and mechanisms of a new phenolic natural product E-[6'-(5'-hydroxypentyl)tricosyl]-4-hydroxy-3-methoxycinnamate (EHHM) isolated fromLivistona chinensison the growth of HCC cells were investigated. It was observed that EHHM treatment significantly suppressed cell proliferation and colony formation, and induced cell apoptosis via a mitochondria-dependent caspase pathway in HepG2 cells in a time- and dose-dependent manner. Meanwhile, EHHM treatment also led to upregulated expression of autophagy protein 5 (Atg5), Beclin 1 and light chain 3 (LC3)-II proteins, and accumulation of green fluorescent protein-LC3 punctate florescent foci in HCC cells, suggesting that EHHM-induced apoptosis is accompanied by autophagy induction. Western blotting revealed that EHHM-induced autophagy is related to the inhibition of the Akt/mechanistic target of rapamycin/p70 ribosomal protein S6 kinase signaling pathway. Furthermore, treatment with Atg5 small interfering RNA or autophagy inhibitors significantly enhanced EHHM-mediated growth inhibition and apoptotic cell death, indicating that autophagy serves as a self-protective mechanism in EHHM-treated HCC cells, and that combined treatment with EHHM and autophagy inhibitors may be an effective therapeutic strategy for HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; Department of Hepatobiliary Surgery, Nanshan Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518000, P.R. China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Sun
authors.affiliation: The Shenzhen Key Laboratory of Gene and Antibody Therapy, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
keywords: EHHM; apoptosis; autophagy; hepatocellular carcinoma