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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
- Source :
- Phytomedicine. 19:779-787
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- 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.
- Subjects :
- Curcumin
Lung Neoplasms
endocrine system diseases
Chemosensitizer
Pharmaceutical Science
Adenocarcinoma of Lung
Apoptosis
Caspase 3
Adenocarcinoma
Pharmacology
chemistry.chemical_compound
Cell Line, Tumor
Drug Discovery
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
STAT3
Protein kinase B
Cell Proliferation
biology
Hypoxia-Inducible Factor 1, alpha Subunit
Complementary and alternative medicine
chemistry
Drug Resistance, Neoplasm
Cell culture
Cancer cell
biology.protein
Molecular Medicine
Cisplatin
Drug Screening Assays, Antitumor
Subjects
Details
- ISSN :
- 09447113
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Phytomedicine
- Accession number :
- edsair.doi.dedup.....d8f9f272f34eac0770b79dee949523f4