Abstract
In this study, we showed that curcumin treatment resulted in activation of Chk1-mediated G2 checkpoint, which was associated with the induction of G2/M arrest and the resistance of cancer cells to curcumin-induced apoptosis. Further investigation revealed that inhibition of Chk1 significantly abrogated G2/M arrest and sensitized curcumin-resistant cells to apoptosis via upregulation of Bad and in turn the loss of mitochondrial membrane potential. These results indicate that Chk1-mediated G2/M arrest may serve as a mechanism for curcumin resistance and Chk1 represents a potential target for the reversal of this resistance. Our findings should be helpful for clinical application of curcumin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis*
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology*
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Cell Division / drug effects
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Cell Line, Tumor
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Checkpoint Kinase 1
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Curcumin / pharmacology*
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Drug Resistance, Neoplasm* / genetics
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G2 Phase / drug effects
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Humans
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology*
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Membrane Potential, Mitochondrial / drug effects
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Up-Regulation
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bcl-Associated Death Protein / genetics
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bcl-Associated Death Protein / physiology
Substances
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Antineoplastic Agents
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bcl-Associated Death Protein
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Protein Kinases
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CHEK1 protein, human
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Checkpoint Kinase 1
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Curcumin