| Curcumin Resistance Induced by Hypoxia in HepG2 Cells Is Mediated by Multidrug-resistance-associated Proteins. | |
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MedLine Citation:
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PMID: 23225435 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: Tumor hypoxia, a common pathophysiological feature of solid tumors, contributes to drug resistance and treatment failure. Here, we demonstrate that hypoxia in HepG2 cells induces resistance towards cytotoxicity of curcumin, a promising anticancer agent. MATERIALS AND METHODS: The number of surviving cells after exposure to chemotherapeutic drugs under normoxia (ambient O(2)) and hypoxia (1% O(2)) was determined by crystal violet staining. The expression levels of drug transporter genes were analyzed by quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: Increased resistance to curcumin, as well as to etoposide and doxorubicin, was observed in HepG2 cells under hypoxia. Gene expression analysis revealed that hypoxia increased the expression of ATP-binding cassette (ABC) drug transporter genes, sub-family C including ABCC1, ABCC2, and ABCC3, by more than two-fold. While expression of ABC drug transporter genes sub-family B member 1 and sub-family G member 2 (ABCB2/P-gp and ABCG2, respectively) did not change significantly. Both inhibitors of ABCC1/ABCC2 and depletion of intracellular glutathione levels were able to reverse hypoxia-induced curcumin resistance. CONCLUSION: ABCC1 and ABCC2 play an important role in hypoxia-induced curcumin resistance in human hepatocellular carcinoma. |
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Authors:
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Titipatima Sakulterdkiat; Chantragan Srisomsap; Rachanee Udomsangpetch; Jisnuson Svasti; Kriengsak Lirdprapamongkol |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Anticancer research Volume: 32 ISSN: 1791-7530 ISO Abbreviation: Anticancer Res. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 5337-42 Citation Subset: IM |
Affiliation:
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Laboratory of Biochemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6, Talat Bang Khen, Laksi, Bangkok 10210, Thailand. kriengsak@cri.or.th. |
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