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Curcumin Resistance Induced by Hypoxia in HepG2 Cells Is Mediated by Multidrug-resistance-associated Proteins.
MedLine Citation:
PMID:  23225435     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Titipatima Sakulterdkiat; Chantragan Srisomsap; Rachanee Udomsangpetch; Jisnuson Svasti; Kriengsak Lirdprapamongkol
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  5337-42     Citation Subset:  IM    
Affiliation:
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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