7,8-Dihydroxy-3-arylcoumarin Induces Cell Death Through S-Phase Arrest in MDA-MB-231 Breast Cancer Cells.

Background/aim: Coumarins remain one of the most versatile classes of compounds for anticancer drug design and discovery. The present study aimed to evaluate the in vitro cytotoxic activity of 7,8-Dihydroxy-3-arylcoumarin derivatives (7a-i) in A549, MDA-MB-231and PC-3 cancer cell lines.

Materials And Methods: Cell viability, cell-cycle progression and regulatory protein expression were evaluated using crystal violet dye-binding assay, flow cytometry and western blot analysis.

Results: 7,8-Diacetoxy-3-(4-nitrophenyl)coumarin (7h) showed the highest cytotoxic activity with CC of 7.51±0.07 μM in MDA-MB-231 cell line. The mechanism of cytotoxic action indicated that 7h caused significant (p<0.05) MDA-MB-231 cells arrest in the S phase as well as moderate cells arrest in the G/M phase; confirmed by up-regulation of cyclins A/B1, p21 and CDKs 4/6, and down-regulation of cyclin E2 and CDK2 regulatory proteins.

Conclusion: These results suggest that 7h could serve as a valuable template for the development of novel synthetic compounds for breast cancer treatment.