Probing the Anticancer and Apoptotic Effects of Kahweol Diterpenoid: Experimental and Theoretical Validation in OVCAR-۳ Human Ovarian Cancer Cells Using Various Bioassays and in Silico Molecular Docking

The incidence of ovarian cancer in China is on the rise, and it remains a leading cause of cancer-related mortality among Chinese women. The main objective of this research work was to probe the anticancer and apoptotic effects of Kahweol in OVCAR-۳ human ovarian cancer cells using various standard bioassays and then theoretically validate the experimental results. MTT assay was used to study the impact of Kahweol on OVCAR-۳ cell viability. Fluorescence microscopy using DAPI, AO/EB, and flow cytometry using annexin-V were used as staining agents for studying Kahweol's effects on cell apoptosis. Effects on cell migration and cell invasion were studied by Transwell assay. AutoDoc-vina using Kahweol as the target ligand and vascular endothelial growth factor receptor-۲ (VEGFR-۲), platelet-derived growth factor receptor (PDGFR), rapidly accelerated fibrosarcoma (Raf), and topoisomerase-I as the target proteins were used to study molecular interactions. Results indicate that Kahweol-induced selective cell viability inhibitory effects against cancer cells in comparison to the normal human Ovarian Surface Epithelialv (OSE) cells. As Kahweol dosage increased, red/yellow fluorescent cells (indicative of apoptosis) increased, and DAPI indicated considerable chromatin condensation and altered cellular morphology. Kahweol-treated cells had a larger proportion of early and late apoptotic cells than untreated cells, according to flow cytometry. Kahweol also inhibited OVCAR-۳ cell migration and invasion, suggesting antimetastatic potential. Kahweol binds to critical aminoacids in target proteins showing binding scores of -۷.۴, -۸.۶, -۸.۰, and -۸.۶ to VEGFR-۲, PDGFR, Raf, and topoisomerase-I, respectively, thereby blocking its expressions. The docking results were validated by calculation of Root Mean Square Fluctuation (RMSF) values which showed stability for most of the legend-receptor interactions. In conclusion, this study sums up that Kahweol exerts anticancer, apoptotic, and inhibition of cell migration and cell invasion and can be considered to be a potent anticancer drug candidate provided further in-depth studies are carried out.

کلیدواژه ها:

Kahweol ، Ovarian Cancer ، Apoptosis ، flow cytometry ، in silico molecular docking