IN-SILICO ANALYSIS OF THYMOQUINONE AS AN ANTI-CANCER AGENT AGAINST CHEMORESISTANCE-ASSOCIATED PROTEINS IN OVARIAN CANCER

Abstract

Thymoquinone (TQ), a polyphenol obtained from Nigella sativa plays a fundamental role in controlling homeostasis. Itpossesses anti-cancer, anti-oxidant, anti-inflammatory, and analgesic properties. Its anti-cancer properties extend tolymphoma, leukaemia, medulloblastoma, prostate, pancreatic, breast, and ovarian cancer (OvCa). OvCa is one of themost lethal malignancies worldwide having distinct symptoms and a poor prognosis. Resistance to Cisplatin (CDDP) andsubsequent reoccurrence of tumors lead to treatment failure. To tackle this, combination therapies along withpolyphenols are being studied and have been proven to enhance CDDP response. Certain proteins such as Bcl-2, Bax,STAT3, p53, and caspase-3/9 are involved in cancer progression and signaling of chemoresistance. In this study,Thymoquinone (TQ) interactions with these proteins have been observed through molecular docking. The 3D structureprediction was carried out using Phyre2 and SWISS-MODEL. The molecular docking of protein targets and TQ wasdone using the PatchDock server. The docked results were then visualized using Discovery Studio. This study helps us tounderstand the interactions between TQ and apoptotic proteins that help in the augmentation of conventional therapy.This knowledge will also help in developing a new approach and alternate therapeutic strategies using polyphenols likeTQ, even in resistant cells.