Open AccessIsocorydine Inhibits Cell Proliferation in Hepatocellular Carcinoma Cell Lines by Inducing G2/M Cell Cycle Arrest and Apoptosis
Author(s) -
Hefen Sun,
Helei Hou,
Ping Lü,
Lixing Zhang,
Fangyu Zhao,
Chao Ge,
Wang Ting-pu,
Ming Yao,
Jinjun Li
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0036808
Subject(s) - cyclin b1 , apoptosis , cyclin dependent kinase 1 , cell cycle checkpoint , cell cycle , cell growth , cell culture , cancer research , hepatocellular carcinoma , cyclin , biology , microbiology and biotechnology , chemistry , biochemistry , genetics
The treatment of human hepatocellular carcinoma (HCC) cell lines with (+)-isocorydine, which was isolated and purified from Papaveraceae sp. plants, resulted in a growth inhibitory effect caused by the induction of G2/M phase cell cycle arrest and apoptosis. We report that isocorydine induces G2/M phase arrest by increasing cyclin B1 and p-CDK1 expression levels, which was caused by decreasing the expression and inhibiting the activation of Cdc25C. The phosphorylation levels of Chk1 and Chk2 were increased after ICD treatment. Furthermore, G2/M arrest induced by ICD can be disrupted by Chk1 siRNA but not by Chk2 siRNA. In addition, isocorydine treatment led to a decrease in the percentage of CD133 + PLC/PRF/5 cells. Interestingly, isocorydine treatment dramatically decreased the tumorigenicity of SMMC-7721 and Huh7 cells. These findings indicate that isocorydine might be a potential therapeutic drug for the chemotherapeutic treatment of HCC.