Antitumor and toxic effects of two derivatives of podophyliotoxin (GP 4 and GP 7) as compared with etopostde (VP 16)

Abstract

Furanodiene is a natural product isolated from Rhizoma curcumae, and exhibits broad-spectrum anticancer activities in vitro and in vivo. Our previous study proved that furanodiene could increase growth inhibition of steroidal agent in ER alpha-positive breast cancer cells, but whether furanodiene can influence ER status is not clear. In this study, we confirmed that furanodiene down-regulated the ER alpha protein expression level and inhibited E2-induced estrogen response element (ERE)-driven reporter plasmid activity in ER alpha-positive MCF-7 cells. Actually, ERoc-knockdown cells were more sensitive than ER alpha positive cells to furanodiene on the cytotoxicity effect. So the anti-cancer effects of furanodiene and non steroidal agent in breast cancer cells still requires further investigation. Our results showed that furanodiene exposure could enhance growth inhibitory effects of doxorubicin in ERoc-negative MDA-MB-231 cells and ER alpha-low expression 4T1 cells. However, furanodiene did not increase the cytotoxicity of doxorubicin in ER alpha-positive breast cancer cells, non-tumorigenic breast epithelial cells, macrophage cells, hepatocytes cells, pheochromocytoma cells and cardiac myoblasts cells. Furanodiene enhances the anti-cancer effects of doxorubicin in ER alpha-negative breast cancer cells through suppressing cell viability via inducing apoptosis in mitochondria-caspases-dependent and reactive oxygen species-independent manners. These results indicate that furanodiene may be a promising and safety natural agent for cancer adjuvant therapy in the future. (C) 2016 Published by Elsevier B.V.