Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/m cell cycle arrest and apoptosis.

Abstract	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.
Authors	Hefen Sun, Helei Hou, Ping Lu, Lixing Zhang, Fangyu Zhao, Chao Ge, Tingpu Wang, Ming Yao, Jinjun Li
Journal	PloS one (PLoS One) Vol. 7 Issue 5 Pg. e36808 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID	22623962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Aporphines Plant Extracts Tetrazolium Salts Thiazoles isocorydine Protein Kinases Checkpoint Kinase 2 CHEK1 protein, human CHEK2 protein, human Checkpoint Kinase 1 Protein Serine-Threonine Kinases thiazolyl blue
Topics	Apoptosis (drug effects) Aporphines (isolation & purification, pharmacology) Blotting, Western Carcinoma, Hepatocellular (drug therapy, physiopathology) Cell Cycle Checkpoints (drug effects) Cell Line, Tumor Cell Proliferation (drug effects) Checkpoint Kinase 1 Checkpoint Kinase 2 Flow Cytometry Humans Liver Neoplasms (drug therapy, metabolism, physiopathology) Papaveraceae (chemistry) Phosphorylation (drug effects) Phytotherapy (methods) Plant Extracts (isolation & purification, pharmacology) Protein Kinases (metabolism) Protein Serine-Threonine Kinases (metabolism) RNA Interference Tetrazolium Salts Thiazoles

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