Furanodiene enhances the anti-cancer effects of doxorubicin on ERα-negative breast cancer cells in vitro

Abstract

Furanodiene is a natural product isolated from Rhizoma curcumae, and exhibits broad-spectrum anti-cancer activities in vitro and in vivo. Our previous study proved that furanodiene could increase growth inhibition of steroidal agent in ERα-positive breast cancer cells, but whether furanodiene can influence ER status is not clear. In this study, we confirmed that furanodiene down-regulated the ERα protein expression level and inhibited E2-induced estrogen response element (ERE)-driven reporter plasmid activity in ERα-positive MCF-7 cells. Actually, ERα-knockdown cells were more sensitive than ERα 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 ERα-negative MDA-MB-231 cells and ERα-low expression 4T1 cells. However, furanodiene did not increase the cytotoxicity of doxorubicin in ERα-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 ERα-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.

Keywords: Apoptosis; Breast cancer; Combination; Doxorubicin; Doxorubicin (PubChem CID: 31703); Formaldehyde (PubChem CID: 712); Furanodiene; Furanodiene (PubChem CID: 636458); H2DCFDA (PubChem CID: 77718); Propidium iodide (PubChem CID: 104981); Tetradecanoylphorbol Acetate (PubChem CID: 27924); Thiazolyl blue (PubChem CID: 64965); tert-Butyl hydroperoxide (PubChem CID: 6410); z-VAD-fmk (PubChem CID: 5737); β-estrogen (PubChem CID: 5757).