AIM: Natural chemopreventives and antioxidants may modulate the response to chemotherapy. In this study we have examined the chemoadjuvant potential of curcumin and quercetin on cisplatin-mediated cell killing/apoptosis, especially the role of mitochondria in the esophageal cancer cell line Hep-2. METHODS: Apoptosis was detected by flow cytometry. The protein expression of mitochondrion-related apoptotic mediators, i.e. Bcl-2, Bcl-X(subscript L), Bax, cytochrome c, and AIF, were studied by Western Blotting. The transcripts of anti-oxidant enzymes were quantitated by RT-PCR. RESULTS: The findings suggest that priming Hep-2 cells with curcumin increased the cisplatin-induced apoptosis by 7.1% whereas priming with quercetin increased it by 16.3%. Curcumin induced apoptosis in Hep-2 cells, which was mediated by an increase in Bax and nuclear AIF and a decrease in Bcl-X(subscript L). Quercetin on the other hand, induced apoptosis through a caspase-3-dependent pathway involving the participation of the proteins Bcl-2, Bcl-X(subscript L), Bax and cytochrome c. The anti-oxidant enzymes Mn-superoxide dismutase, Cu-Zn superoxide dismutase, glutathione peroxidase, and catalase did not show any significant increase at the transcriptional level in case of combination of curcumin or quercetin with cisplatin. CONCLUSION: The data suggests that priming with curcumin or quercetin may improve the efficacy of chemotherapy for head and neck cancer by inducing apoptosis through the mitochondrial pathway, thus minimizing the side effects associated with combination chemotherapy.
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