Salinomycin overcomes acquired tamoxifen resistance through AIB 1 and inhibits cancer cell invasion in endocrine resistant breast cancer

• Published in: Clinical and experimental pharmacology & physiology Vol. 44; no. 10; pp. 1042 - 1052
• Main Authors: Manmuan, Suwisit, Sakunrangsit, Nithidol, Ketchart, Wannarasmi
• Format: Journal Article
• Language: English
• Published: 01.10.2017
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12806

Summary Salinomycin is a monocarboxylic polyether ionophore isolated from Streptomyces albus . It has been widely used as an antibiotic in veterinary medicine in poultry. A recent study demonstrated that salinomycin selectively inhibits human breast cancer stem cells; one possible mechanism of tamoxifen resistance. Our results show that salinomycin is effective in inhibiting MCF ‐7/ LCC 2 and MCF ‐7/ LCC 9 cell lines which are well‐established endocrine resistant cells and has a synergistic effect in combination with tamoxifen using MTT proliferation assay. The inhibitory effect of salinomycin on the reduction of critical ER co‐activator; amplified breast 1 ( AIB 1 ) mRNA and protein expression is overcoming tamoxifen resistance . Moreover, salinomycin significantly inhibits cell invasion in Matrigel invasion assay. The effect was mediated at least in part by the decrease of matrix metalopeptidase 9 ( MMP ‐9) which is one critical enzyme facilitated in the cell invasion process. In conclusion, salinomycin should be developed as a novel agent used alone or in combination for endocrine‐resistant breast cancer.