PDE5 inhibitor potentiates the 67 kDa Laminin Receptor-mediated anti-inflammatory and anticancer activity of Polyphenols

Abstract

Background: 67-kDa laminin receptor is a cell surface receptor for laminin and polyphenols like EGCG. 67LR overexpressed in different cancers. Polyphenols-induced activation of 67LR activates Akt/eNOS/NO/cGMP/PKCδ pathways very well known for apoptotic signalling and inhibits cell growth via PKA/PP2A activation, ultimately triggering cancer cell death. The binding of EGCG to the Human laminin receptor (67LR) upregulates Tollip expression, inhibits TLR4 signaling, and prevents inflammation. Method: Protein-ligand docking was performed considering Human laminin receptor (67LR) precursor (PDB ID - 3BCH) as protein and 18 polyphenols as ligand using Autodock Vina 1.1.2. Result: combining EGCG or other potent polyphenols with PDE5 inhibitors may impart a rationale for the clinical efficiency of this formulation for cancer therapeutics and 67LR is conceivably an absolute novel target for cancer chemotherapy and treatment of inflammation. Discussion: Developing the anticancer formulation of the anticancer drug, 67LR inducer along with inhibitor of PDE5 and SET could exert strong antitumor effects via the 67LR. It will reduce the dose of anticancer drugs and adverse side effects.