Role of mitochondria in quercetin-enhanced chemotherapeutic response in human non-small cell lung carcinoma H-520 cells.
Dietary phytochemicals have been shown to be chemopreventive against various types of cancer. This study was designed to investigate the enhancement of the chemoresponse to cisplatin by quercetin in human lung cancer H-520 cells and to elucidate the role of mitochondria in the induction of apoptosis. Apoptosis was detected by flow cytometry. The protein expressions of Bcl-XL, Bcl-2, Bax, cytochrome c and AIF were studied by Western blotting. The transcription of antioxidant enzymes was quantitated by RT-PCR. The findings suggested that priming H-520 cells with quercetin increased the cisplatin-induced apoptosis by 30.2%. This was accompanied by down-regulation of Bcl-XL and Bcl-2 and up-regulation of Bax. Both cytochrome c and AIF were implicated in the apoptotic process. There was no significant change in the transcription level of antioxidant enzymes in quercetin-mediated apoptosis. Based on these findings, it can be concluded that quercetin might act as an effective chemosensitizer in the chemotherapy of lung cancer by regulating the expression of various apoptosis-related genes.
Kuhar
Meenakshi
M
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Sen
Sudip
S
Singh
Neeta
N
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D011794:Quercetin; D002945:Cisplatin