The antagonistic atorvastatin-glibenclamide interactions suppressed the atorvastatin-induced Bax/cytochrome c/p53 mRNA expressions and increased Rho A mRNA expression in B16f10 melanoma cell culture

Abstract

Many studies have shown promising benefits for using statins among cancer patients. Here, we considered the effects of atorvastatin-glibenclamide interactions on pro-apoptotic and metastatic factors of Bax, p53, cyto-chrome c and Rho A genes in melanoma cell cancer. Melanoma B16F10 cells were treated for 48 h with glibenclamide and atorvastatin alone and glibenclamide-atorvastatin combination followed by quantitative RTPCR assay. Cells with no treatment were considered as control. Results revealed an increase in the expression of Bax, cytochrome c and p53 mRNAs in atorvastatin group without any changes in Rho A gene expression. In contrast to, glibenclamide increased Rho A gene expression and suppressed cytochrome c expression by decreasing Bax level. Effects of combination therapy on atorvastatin-induced increase in Bax/cytochrome c/p53 mRNA expression depended on glibenclamide concentration. Glibenclamide at low concentrations of 1 mu M and 10 mu M suppressed atorvastatin-induced increase in Bax/cytochrome c/p53 mRNA and promoted metastatic signal of Rho A in melanoma cells, while glibenclamide at high concentration of 100 mu M induced an increase in mRNA expression of cytochrome c and p53 in melanoma cells. Together, our study provides evidence that the anticancer effect of statins on melanoma could be antagonized by associated sulfonylureas use.