Journal
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
Volume 44, Issue 10, Pages 1042-1052Publisher
WILEY
DOI: 10.1111/1440-1681.12806
Keywords
breast cancer; resistance; salinomycin; tamoxifen
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Funding
- Ratchadaphiseksomphot Endowment Fund for new staff development [GDNS 56-052-30-008]
- Special Task Force for Activating Research (STAR) Ratchadaphiseksomphot Endownment fund to Overcoming Cancer Drug Resistance Research group [GSTAR 59-005-30-001]
- 90th Anniversary of Chulalongkorn University Fund [GCUGR11255725073M]
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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/LCC2 and MCF-7/LCC9 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 (AIB1) 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.
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