Naringenin promote apoptosis in cerebrally implanted C6 glioma cells
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Naringenin (NGEN), a naturally occurring citrus flavonone, has shown cytotoxicity in various human cancer cell lines as well as inhibitory effects on tumor growth. It has been also shown to access the brain and there is an increasing interest in its therapeutic applications. The up-regulated expression of Cx43 leads to the suppression of tumorigenicity with promoted apoptotic events. In this study, we investigated the in vivo effect of NGEN in fostering apoptosis in cerebrally implanted C6 glioma cells rat model. We analysed the expression of Cx43, caspase-3, caspase-9, Cyt C, Bcl-2 and Bax in vivo by immunoblot analysis and the ultra structure of brain cells by transmission electron microscopy. Supplementation of NGEN to experimental animals modulated Bcl-2/Bax ratio and up-regulation of caspase-3 and 9. NGEN was also found to up-regulate the expression of Cx43. These findings provide evidence that NGEN’s apoptotic effect, modulation of Bcl-2/Bax ratio leads to release of Cyt C from mitochondria, thereby activation of caspase-3 and caspase-9 is mediated by enhanced expression of Cx43. These observations were well supported by the transmission electron microscopic results which showed the characteristic apoptotic features. In conclusion, our findings demonstrate that NGEN promotes apoptosis in rat C6 glioma model.
KeywordsC6 glioma Naringenin Cx43 Apoptosis Bcl-2 Bax Cyt C Caspase-3 Caspase-9
- 16.Gayathri R, Gunadharini DN, Arunkumar A, Senthilkumar K, Krishnamoorthy G, Banudevi S, Vignesh RC, Arunakaran J (2009) Effects of diallyl disulfide (DADS) on expression of apoptosis associated proteins in androgen independent human prostate cancer cells (PC-3). Mol Cell Biochem 320:197–203CrossRefPubMedGoogle Scholar
- 22.Fiddo RJ, Tatham AS, Shewry PR (1995) Western blotting analysis. Methods Mol Biol 49:423–437Google Scholar
- 26.Vijayababu MR, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas MM, Arunakaran J (2005) Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. J Cancer Res Clin Oncol 131:765–771CrossRefPubMedGoogle Scholar
- 27.Sabarinathan D, Vanisree AJ (2010) Naringenin, a flavanone alters the tumorigenic features of C6 glioma cells. Biomed Pharmacother (in press)Google Scholar