Mechanism Underlying the Inhibitory Effect of Bio-synthesized Silver Nanoparticle on TNF-α induced NF- κB Nuclear Translocation in Prostate Cancer Cells

Abstract

Apoptosis, a physiological mechanism of highly orchestrated cell death, can be initiated by extracellular and intracellular mechanisms that trigger a complex machinery of proapoptotic proteases and mitochondrial changes, leading to the activation of specific endonucleases and DNA fragmentation. The present study was undertaken to elucidate a mechanism underlying the inhibitory effect of biosynthesised silver nanoparticle on TNF-α induced NF-κB nuclear translocation in prostate cancer PC- 3 cells. The  cell cycle analysis of Prostate cancer PC-3 cells was examined by flow cytometry by using annexin V-FITC/PI staining. Effect of silver nanoparticles in oxidative stress ROS, Effect of biosynthesized silver nanoparticle on apoptosis in human prostate cancer cell line and apoptotic induction of TNF-α and NF-κB expression was studied by Flow cytometry in Prostate cancer PC-3 cell line. From the results it was observed that biosynthesized silver nanoparticle inhibits the cellular growth of human prostate cancer PC-3 cells and induces apoptosis. The ROS levels generated in response to silver nanoparticles were significantly higher in treated PC-3 cells than the control. The result indicates that cell death is mediated by ROS production, which might alter the cellular redox status, and it is a potential reason for cell death. Apoptosis of the silver nanoparticle treated PC-3 cells was accompanied by a reduction in the percentage of cells in G0/G1 phase and an increase in the percentage of G2/M phase cells, indicating cell cycle arrest at G2/M phase, and transcription factor NF-κB plays an essential role in inflammation and cancer. The activation of NF-κB in response to inflammatory cytokine such as TNF-α promotes nuclear migration to enable DNA-binding activity and facilitate target genes expression.