Lamia Hamdan Ramdani1,2, Oualid Talhi3,4, Caroline Decombat2, Marion Vermerie2, Alexandre Berry2, Artur Silva4, Khaldoun Bachari3, Marie-Paule Vasson2,5, Laetitia Delort2, Florence Caldefie-Chézet2,6. 1. Scientific and Technical Research Center in Physico-Chemical Analysis (CRAPC), Tipaza, Algeria lamia_pharm@yahoo.fr. 2. Clermont Auvergne University, INRA, UNH, Human Nutrition unit, CRNH Auvergne, Clermont Ferrand, France. 3. Scientific and Technical Research Center in Physico-Chemical Analysis (CRAPC), Tipaza, Algeria. 4. Organic Chemistry, Natural Products and Agrifood (QOPNA), Department of Chemistry & QOPNA, University of Aveiro, Aveiro, Portugal. 5. Anticancer Center Jean-Perrin, Clermont Ferrand, France. 6. CLARA, Lyon Auvergne Rhone Alpes canceropole, Lyon, France.
Abstract
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 μM, 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. Copyright
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 μM, 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. Copyright