Piceatannol Enhances the Antitumor Efficacy of Gemcitabine in Human A549 Non-Small Cell Lung Cancer Cells.
To enhance the anticancer efficacy of gemcitabine in the treatment of non-small cell lung cancer (NSCLC), the potential synergistic effect of piceatannol on gemcitabine cytotoxicity was investigated in the human NSCLC A459 cell line. The MTT cell viability assay showed that piceatannol significantly enhanced the cytotoxic effects of gemcitabine by lowering the gemcitabine IC50 value. Flow cytometry analysis revealed that piceatannol exerted its pharmacological effect mainly by increasing the late apoptotic population. Western blot analysis showed that gemcitabine induced the expression of the proapoptotic proteins Bad and Bak, and pretreatment with piceatannol further increased Bak expression, leading to an increased number of cells undergoing late apoptosis. The findings from this study show that piceatannol can enhance the cytotoxic effects of gemcitabine by enhancing expression of the proapoptotic protein Bak, thereby providing the rational basis for a novel combination strategy for the treatment of NSCLC.
Department of Oncology, Wuhan University Renmin Hospital, Wuhan, Hubei, P.R. China.
Bin
B
Xu
Ze-Zhang
ZZ
Tao
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism; D000093542:Gemcitabine
C494819:BAD protein, human; C494772:BAK1 protein, human; D013267:Stilbenes; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051025:bcl-Associated Death Protein; D003841:Deoxycytidine; C041525:3,3',4,5'-tetrahydroxystilbene; D000093542:Gemcitabine