Inhibition of DDX3 and COX-2 by forskolin and evaluation of anti-proliferative, pro-apoptotic effects on cervical cancer cells: molecular modelling and in vitro approaches.

Abstract

Several studies have reported up-regulation of both cyclooxygenase-2 (COX-2) and DEAD-box RNA helicase3 (DDX3) and have validated their oncogenic role in many cancers. Inhibition of COX-2 and DDX3 offers a potential pharmacological strategy for prevention of cancer progression. The COX-2 isoform is expressed in response to pro-inflammatory stimuli in premalignant lesions, including cervical tissues. This study elucidates the potential role of plant derived compound Forskolin (FSK) in plummeting the expression of COX-2 and DDX3 in cervical cancer. To establish this, the cervical cancer cells were treated with the FSK compound which induced a dose dependent significant inhibition of COX-2 and DDX3 expression. The FSK treatment also significantly induced apoptosis in cancer cells by modulating the expression of apoptotic markers like caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, full length-poly ADP ribose polymerase (PARP), cleaved-poly ADP ribose polymerase (C-PARP) and Bcl2 in dose dependent manner. Further FSK significantly modulated the cell survival pathway Phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway upon 24h of incubation in cervical cancer cells. The molecular docking studies revealed that the FSK engaged the active sites of both the targets by interacting with key residues.