title: 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.
authors.affiliation: Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, China.
authors.forename: Zhang-Feng
authors.initials: ZF
authors.lastname: Zhong
authors.affiliation: Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.
authors.forename: Wen-An
authors.initials: WA
authors.lastname: Qiang
authors.affiliation: Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, China.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou, Gansu, China. Electronic address: tanwen@lzu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.affiliation: Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau, China. Electronic address: ytwang@umac.mo.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology*; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D008264:Macrophages / Q000187:drug effects; D032446:Myoblasts / Q000187:drug effects; D010673:Pheochromocytoma / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D017382:Reactive Oxygen Species; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C442489:furanodiene; D004317:Doxorubicin
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)