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Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF-1α and caspase-3 mechanisms.
MedLine Citation:
PMID:  22483553     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Curcumin, a yellow pigment derived from Curcuma longa Linn, has been favored by the Eastern as dietary ingredients for centuries. During the past decade, extensive investigations have revealed curcumin sensitized various chemotherapeutic agents in human breast, colon, pancreas, gastric, liver, brain and hematological malignant disorders in vivo and in vitro. Several pathways and specific targets including NF-κB, STAT3, COX-2, Akt and multidrug resistant protein have been identified to facilitate curcumin as a chemosensitizer. Recent studies suggest HIF-1α participated in the development of drug resistance in cancer cells and targeting HIF-1α either by RNAi or siRNA successfully overcame chemotherapeutic resistance. To investigate the mechanism basis of curcumin as a chemosensitizer in lung cancer, we examined curcumin's effects on HIF-1α in cis-platin (DDP) sensitive A549 and resistant A549/DDP cell lines by RT-PCR and Western blot. HIF-1α in A549/DDP cells was found to be overexpressed at both mRNA and protein levels together with a poor response to DDP. Results from transient transfection and flow cytometry showed the HIF-1α abnormality contributed to DDP resistance in A549/DDP lung cancer cells. Combined curcumin and DDP treatment markedly inhibited A549/DDP cells proliferation, reversed DDP resistance and triggered apoptotic death by promoting HIF-1α degradation and activating caspase-3, respectively. Expression of HIF-1α-dependent P-gp also seemed to decrease as response to curcumin in a dose-dependent manner. Our findings shed light on drug resistant reversing effect of curcumin in lung cancer cells by inhibiting HIF-1α expression and activating caspase-3.
Authors:
Ming-Xiang Ye; Yi-Lin Zhao; Yan Li; Qing Miao; Zhi-Kui Li; Xin-Ling Ren; Li-Qiang Song; Hong Yin; Jian Zhang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-4
Journal Detail:
Title:  Phytomedicine : international journal of phytotherapy and phytopharmacology     Volume:  -     ISSN:  1618-095X     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9438794     Medline TA:  Phytomedicine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.
Affiliation:
Department of Pulmonary Medicine, Detection Center for Tumor Biomarker, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
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