Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation.
The purpose of this study was to investigate the sensitizing effect of curcumin on cisplatin-induced apoptosis in non-small cell lung cancer (NSCLC) H460 cells. Curcumin was shown to induce superoxide anion generation, down-regulate anti-apoptotic Bcl-2 protein, and subsequently sensitize cells to cisplatin-induced apoptosis. Co-treatment of the cells with curcumin and cisplatin resulted in increased apoptosis and reversal of Bcl-2-mediated cisplatin resistance. The mechanism by which curcumin down-regulates Bcl-2 and sensitizes cells to cisplatin-induced apoptosis involves proteasomal degradation of Bcl-2. These findings indicate a novel pathway for curcumin regulation of Bcl-2, which could benefit the development of a cisplatin sensitizing agent.
Chanvorachote
Pithi
P
Department of Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, Thailand. pithi_chan@yahoo.com
Pongrakhananon
Varisa
V
Wannachaiyasit
Sumalee
S
Luanpitpong
Sudjit
S
Rojanasakul
Yon
Y
Nimmannit
Ubonthip
U
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D019253:Proto-Oncogene Proteins c-bcl-2; D013481:Superoxides; D046988:Proteasome Endopeptidase Complex; D003474:Curcumin; D002945:Cisplatin