Naringenin promote apoptosis in cerebrally implanted C6 glioma cells.
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.
Sabarinathan
Devan
D
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, Tamilnadu, India.
Mahalakshmi
Palani
P
Vanisree
Arambakkam Janardhanam
AJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000187:drug effects; D020169:Caspases / Q000032:analysis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000637:transplantation; D054022:Cerebrum / Q000473:pathology*; D004965:Estrogen Antagonists; D044950:Flavanones / Q000494:pharmacology*; D047309:Flavones; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats
D051017:Apoptosis Regulatory Proteins; D004965:Estrogen Antagonists; D044950:Flavanones; D047309:Flavones; D020169:Caspases; C005273:naringenin; C043562:flavone