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.
Original language | English (US) |
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Pages (from-to) | 10-19 |
Number of pages | 10 |
Journal | European Journal of Pharmacology |
Volume | 774 |
DOIs | |
State | Published - Mar 5 2016 |
Funding
This study was supported by the Macao Science and Technology Development Fund ( 077/2011/A3 and 048/2013/A2 ), and the Research Fund of University of Macau ( CPG2014-00012-ICMS , UL016/09Y4/CMS/WYT01/ICMS and MYRG208 (Y3-L4)-ICMS11-WYT ). We extremely thank Dr. Xiu-Ping Chen, Dr. Jin-Jian Lu, Dr. Jian-Li Gao, and all from the University of Macau, for their technical help.
Keywords
- Apoptosis
- Breast cancer
- Combination
- Doxorubicin
- Furanodiene
ASJC Scopus subject areas
- Pharmacology