AR independent anticancer potential of enza against prostate cancer

Abstract

The survival rate of metastatic castrate resistance prostate cancer (CRPC) patient can be improved by the second-generation anti-androgen drugs such as enzalutamide (enza). But unfortunately, CRPC patients do respond with enza in the beginning and become resistance in due course of time against this drug. Therefore, in the given investigation, enza was delivered to the AR-null cells (PC3 & DU145) via EnSvGNPs (enza bioconjugated survivin polyclonal antibodies encapsulated gold nanoparticles) where SvGNPs (survivin polyclonal antibodies encapsulated gold nanoparticles), as a delivery vehicle, has also got anticancer potential and was found to act synergistically with enza. The confirmation of synthesis and characterizations of biosynthesized EnSvGNPs & SvGNPs were done by using different physical techniques. Survivin, an anti-apoptotic protein was selected to deliver EnSvGNPs via survivin antibodies selectively in the prostate cancer cells because it is over expressed in various types of cancer cells but not in normal cells. The efficacy of enza was also found to increase due to synergistic effect along with SvGNPs where each component of the system potentiated the effect of each other and successfully reduced the effective concentration of each component mutually with patient compliance. Each component of the system targeted different pathway(s) to check the growth of cancer cells. The EnSvGNPs were found safe against NRK cell line. This novel and smart targeted delivery system successfully inhibited the propagation of DU145 (IC50 - 8.21 µM) & PC3 (IC50−12.3 µM) cells through AR independent pathways. Different biological parameters, such as cell viability, proliferation, ROS generation, nuclear condensation, membrane potential variation, Cas-3 activity, and apoptosis were assessed.