A dock derived compound against laminin receptor (37 LR) exhibits anti-cancer properties in a prostate cancer cell line model

Abstract

// Charles Samuel Umbaugh 1 , Adriana Diaz-Quiñones 1 , Manoel Figueiredo Neto 1 , Joseph J. Shearer 1 and Marxa L. Figueiredo 1 1 Department of Basic Medical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, IN 47907, USA Correspondence to: Marxa L. Figueiredo, email: mlfiguei@purdue.edu Keywords: laminin receptor, drug discovery, prostate cancer, anti-cancer compound Received: April 13, 2017      Accepted: July 16, 2017      Published: December 13, 2017 ABSTRACT Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37 LR). 37/67 LR is a strong clinical correlate for progression, aggression, and chemotherapeutic relapse of several cancers including breast, prostate, and colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further increased by its ability to transduce physiochemical and mechanosensing signals in endothelial cells and modulate angiogenesis. Recently, it was demonstrated that 37/67 LR modulates the anti-angiogenic potential of the secreted glycoprotein pigment epithelium-derived factor (PEDF). Restoration of PEDF balance is a desirable therapeutic outcome, and we sought to identify a small molecule that could recapitulate known signaling properties of PEDF but without the additional complications of peptide formulation or gene delivery safety validation. We used an in silico drug discovery approach to target the interaction interface between PEDF and 37 LR. Following cell based counter screening and binding validation, we characterized a hit compound’s anti-viability, activation of PEDF signaling-related genes, anti-wound healing, and anti-cancer signaling properties. This hit compound has potential for future development as a lead compound for treating tumor growth and inhibiting angiogenesis.