Bis(4-hydroxy-2H-chromen-2-one) Coumarin Induces Apoptosis in MCF-7 Human Breast Cancer Cells Through Aromatase Inhibition.

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.

• Authors: Lamia Hamdan Ramdani, Oualid Talhi, Caroline Decombat, Marion Vermerie, Alexandre Berry, Artur Silva, Khaldoun Bachari, Marie-Paule Vasson, Laetitia Delort, Florence Caldefie-Chézet
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 11 Pg. 6107-6114 (Nov 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 31704838 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Biomarkers, Tumor
• Chromones
• Coumarins
• bis(4-hydroxy-2H-chromen-2-one)
• coumarin
• Aromatase
• CYP19A1 protein, human

Topics

• Apoptosis (drug effects)
• Aromatase (chemistry, genetics, metabolism)
• Biomarkers, Tumor (genetics, metabolism)
• Breast Neoplasms (drug therapy, enzymology, genetics, pathology)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Chromones (chemistry)
• Coumarins (chemistry, pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Tumor Cells, Cultured