Pharmacoinformatic screening of phytoconstituent and evaluation of its anti-PDAC effect using in vitro studies

With no prominent treatment for pancreatic ductal adenocarcinoma (PDAC) in conventional chemotherapy, recent studies have focused on uniting conventional and traditional medicines including plant phytoconstituents. Herein, we used pharmacoinformatic studies to identify potent phytoconstituent as ligand having inhibition activities against canonical anticancer targets, and evaluated its effect on PDAC cell lines. SwissTargetPrediction and SuperPred tools were utilized to segregate protein targets of ligand in humans, following which FunRich was applied to garner its targets in PDAC. STRING analysis predicted protein–protein interactions and dynamic simulation studies confirmed stability of ligand–protein complex. For in vitro cytotoxic potential, ligand treatment at different concentrations was given to PDAC cell lines both alone and combined with gemcitabine, followed by evaluation of effects on migration. Differential gene expression was checked using PCR for evaluating mechanism of cytotoxicity. Results showed pentagalloylglucose (PGG) with highest docking and MMGBSA scores for Cyclooxygenase 2 (Cox2) inhibition site. SwissTargetPrediction and SuperPred analysis detected 40 targets of PGG in PDAC. Simulation data showed stability of protein–ligand complex. In in vitro experiments Mia-PaCa-2 was more sensitive to PGG than Panc-1. PGG successfully inhibited migration both alone and in combination with gemcitabine. Additionally, PGG treatment induced apoptosis in both the cell lines; but showed antagonism when combined with gemcitabine. In conclusion, our report demonstrates PGG has good binding with Cox2 and showed anti-PDAC activity by inhibiting migration and inducing apoptosis, thus it can be used as a therapy option. But further studies are required to confirm its behaviour as a combination therapy drug. Communicated by Ramaswamy H. Sarma