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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Aporphines / isolation & purification
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Aporphines / pharmacology*
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Blotting, Western
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / physiopathology
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Cell Cycle Checkpoints / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Checkpoint Kinase 1
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Checkpoint Kinase 2
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Flow Cytometry
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Humans
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / metabolism*
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Liver Neoplasms / physiopathology
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Papaveraceae / chemistry
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Phosphorylation / drug effects
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Phytotherapy / methods*
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology*
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / metabolism
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RNA Interference
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Tetrazolium Salts
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Thiazoles
Substances
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Aporphines
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Plant Extracts
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Tetrazolium Salts
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Thiazoles
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isocorydine
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Protein Kinases
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Checkpoint Kinase 2
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CHEK1 protein, human
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CHEK2 protein, human
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Checkpoint Kinase 1
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Protein Serine-Threonine Kinases
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thiazolyl blue