Dihydroquercetin (DHQ) has the potential to promote apoptosis in ovarian cancer cells: An in silico and in vitro study

Abstract

Ovarian cancer is the third leading gynaecological malignancy that leads to death in females annually. According to the GLOBOCAN 2020 incidence cases in Asia, there were a total of 100,854 ovarian cancer incidence cases. The Food and Drug Administration (FDA) has approved some drug compounds from both the generic and pharmaceutical brands for ovarian cancer, however, these synthetic compounds have many adverse effects such as – infections, fatigue, nerve problems, alopecia (hair loss), weight loss, lack of appetite, chemobrain (forgetfulness). By exploring both the in silico and in vitro aspects, we suggest that dihydroquercetin (DHQ) or simply taxifolin is an effective herbal compound that is druggable, leadlike, has good bioavailability, medicinal chemistry with a higher solubility with no adverse side effects, and toxicity. It also showcased a greater and more stable binding affinity and energy landscape with target POTEE with minimal energy frustrations and clashes. Our study also was able to predict a positive classification model of DHQ with a Tanimoto-distance threshold (d0 = 0.8) and smoothing factor (h = 0.9). We observed that the accuracy decreases to 90% from 100% at distance = 0.7, predicted number of compounds rose from 80 to 95%, which can be worth the loss of accuracy. Furthermore, our in vitro analysis on SK-OV-3 cell lines showcased that the anticancerous activity of DHQ caused significant cancer cell death and cell proliferation at 100 µm and 250 µm solutions. The DHQ drug dosages were further verified by Calcein-AM-PI live dead cell imaging on both concentrations. We observed that at 250 µm, DHQ caused apoptosis in SK-OV-3 cells. Hence, it is concluded that DHQ reduces ovarian cell proliferation and eventually cell death (apoptosis) in ovarian cancer.