Pycnogenol's Dual Impact: Inducing Apoptosis and Suppressing Migration via Vascular Endothelial Growth Factor/Fibroblast Growth Factor Signaling Pathways in Breast Cancer Cells.

Abstract

The leading cause of cancer-related fatalities in women globally is breast cancer. Chemotherapy is one of the traditional therapies for breast cancer, even though it does not target cancer cells directly and has major side effects. As a result, the development of novel therapeutic techniques with improved safety and effectiveness is constantly required. This study aimed to investigate the pro-apoptotic and anti-migrative effects of pycnogenol in a breast cancer cell line. By using the3-[4,5-dimethylthiazol-2-yl]-2,5diphenyl tetrazolium bromide (MTT) method, the cell viability of breast cancer cells treated with pycnogenol was evaluated. Pycnogenol was applied to the MCF-7 cells in a range of concentrations (20-120 µg/ml) for 24 hours. A phase contrast microscope is used to evaluate changes in cell morphology. In breast cancer cells, acridine orange (AO) and ethidium bromide (EtBr)dual staining were employed to analyze the nuclear morphological alterations. A fluorescent microscope was used to see the apoptotic nuclei. A scratch wound healing assay was performed to evaluate the anti-migrative potential of pycnogenol. Gene expression analysis was performed using quantitative real-time PCR to determine the levels of proapoptotic and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) genes mRNA expression. Results:In our investigation, breast cancer cells treated with pycnogenol displayed a substantial reduction in cell viability and a statistically significant p<0.05 between the control and treatment groups. We observed inhibitory concentrations (IC-50) at 80 μg/mL in breast cancer cells. After treatment, fewer cells were present, and those that were there shrank and showed cytoplasmic membrane blebbing. Under AO/EtBr staining, treated cells show chromatin condensation and nuclear fragmentation. The results of this study revealed a significant downregulation of Bcl-2, VEGF/FGF, and p53 mRNA expression following treatment with pycnogenol. Furthermore, the impact of pycnogenol on cell migration decreased significantly when compared to control cells. Pycnogenol treatment significantly induces apoptosis and inhibits migration by altering the VEGF signaling pathway. Conclusion:Overall, this study highlights the promising role of pycnogenol as a proapoptotic and antimigrative agent through the inhibition of anti-apoptotic and VEGF/FGF signaling molecules gene expression, offering new prospects for improving breast cancer treatment.