Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition
2019
Ramdani, L. H. | Talhi, O. | Decombat, Caroline | Vermerie, M | Berry, Alexandre | Silva, A. | Bachari, K. | Vasson, Marie-Paule | Delort, Laetitia | Caldefie-Chezet, Florence | Centre de Recherche Scientifique et Technique en Analyses Physico-Chimiques | Unité de Nutrition Humaine (UNH) ; Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]) | Université Clermont Auvergne [2017-2020] (UCA [2017-2020]) | Department of Chemistry & QOPNA ; Organic Chemistry, Natural Products and Agrifood (QOPNA) | Universidade de Aveiro = University of Aveiro | Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP) ; UNICANCER | Cancéropôle Lyon Auvergne Rhône-Alpes
AIM: The present investigation aimed to examine the therapeutic potential of the new coumarin derivative bis(4-hydroxy-2H-chromen-2-one) coumarin (4HC) against breast cancer. MATERIALS AND METHODS: For this purpose, the effects of 4HC treatment on the proliferation of MCF-7 breast cancer cells and on MCF-10a non-cancerous cells were evaluated using a fluorescent assay. Cell cycle distribution and apoptosis were measured by image cytometry. The expression level of aromatase (CYP19A1) and apoptosis-related genes were determined by real-time PCR. RESULTS: MCF-7 mammary cancer cell proliferation was significantly decreased within 24 h after treatment with 4HC at 50 muM, while no effect was observed on the viability of MCF-10a non-cancerous mammary cells. 4HC also increased the percentage of the cells in the G2/M phase, inducing apoptosis. Real-time PCR revealed that 4HC induced MCF-7 mortality through an up-regulation of Bax and a down-regulation of Bcl-2, resulting in an increase in caspase-3 gene expression. The increased expression of apoptosis-related genes was accompanied by a decrease in CYP19A1 gene expression. CONCLUSION: 4HC selectively inhibits proliferation of MCF-7cells in vitro. Moreover, 4HC has inhibitory effects on aromatase gene expression and promoting effects on apoptosis, in MCF-7 cells.
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