title: 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.affiliation: State Key Laboratory of Oncogenes & Related Genes, Shanghai Cancer Institute, Renji Hospital, Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hefen
authors.initials: H
authors.lastname: Sun
authors.forename: Helei
authors.initials: H
authors.lastname: Hou
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Lixing
authors.initials: L
authors.lastname: Zhang
authors.forename: Fangyu
authors.initials: F
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Ge
authors.forename: Tingpu
authors.initials: T
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001060:Aporphines / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000503:physiopathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D028101:Papaveraceae / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D001060:Aporphines; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; C030168:isocorydine; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; C022616:thiazolyl blue