Screening of MMP-2 Inhibiting Phytoconstituents for the Development of Newer Pancreatic Cancer Treatment Modalities.

Abstract

Pancreatic cancer metastasis is characterized by a higher incidence of morbidity and mortality. The present study attempts to identify phytocomponents with the potential to inhibit the secretion of MMP-2 by pancreatic cancer cells and ascertain the efficacy of individual components. Overall survival analysis carried out revealed reduced survival of patients with high MMP-2 expression. Data analysis from TCGA revealed increased MMP-2 expression in pancreatic cancer patients compared to adjacent normal tissues. The expression of MMP-2 was reported at different stages of pancreatic cancer (Stage I-IV). To understand the relevance of phytocomponents in binding to the catalytic site of MMP-2, molecular docking studies were performed to find the effectiveness based on Glide score/energy. To substantiate the in-silico analysis, the eight components were also tested in vitro for reducing the survival in PANC-1 cells at three different time points (24, 48, and 72 hours). Finally, zymography analysis was performed using the eight components in the PANC-1 conditioned media of treated cells to ascertain the enzymatic activity of MMP-2. The obtained results suggest plumbagin, emodin, and EGCG exert potential inhibition in PANC-1 cells, among other phytocomponents tested. Therefore, as assessed using computational studies, the binding ability of plumbagin, emodin, and EGCG can be interpreted as inhibiting effects on MMP-2 activities. These compounds could find potential application in preventing the progression, sustenance, and metastasis of pancreatic cancer and need to be explored further using a pre-clinical model system in order to validate the efficacy, bioavailability, and safety.