title: (-)-Curine induces cell cycle arrest and cell death in hepatocellular carcinoma cells in a p53-independent way.
abstract: Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide, however, drug resistance is still a tough problem of it. As in many other cancers, p53 mutations are commonly observed in HCCs (Hussain et al., 2007; Levine et al., 1994) [1,2]. Tumor tissues with mutant p53 seems to be more aggressive and resist to chemotherapy than that harboring wide-type p53 (Harris and Hollstein, 1994; Parrales and Iwakuma, 2015) [3,4]. (-)-Curine, a novel bisbenzylisoquinoline alkaloid, is one of the main components isolated from the roots of Cyclea wattii. Here, it was found to exert cytotoxity on hepatocellular carcinoma (HCC) cells regardless of p53 status. We found that (-)-curine induced G1 arrest and cell death in HepG2 cells with wild-type p53 as well as Huh-7 cells with mutant p53. In HepG2 cells, knocking down of p53 did not change its cellular responses to (-)-curine, and same degree of G1 arrest and cell death were occurred after p53 knockdown. Taken together, our data demonstrate that (-)-curine can inhibit viability of hepatocellular carcinoma cells in regardless of p53 status. It shed light on new therapy methods for HCC.
authors.affiliation: College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Gong
authors.affiliation: College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xu
authors.affiliation: College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China. Electronic address: fundzou@scu.edu.cn.
authors.forename: Fangdong
authors.initials: F
authors.lastname: Zou
authors.affiliation: College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China. Electronic address: pengrui@ymail.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007546:Isoquinolines; C470478:curine
keywords: (−)-Curine; Cell cycle arrest; Cell death; Hepatic carcinoma