Skip Navigation

Publication Detail

Title: Induction of endoplasmic reticulum stress might be responsible for defective autophagy in cadmium-induced prostate carcinogenesis.

Authors: Kolluru, Venkatesh; Tyagi, Ashish; Chandrasekaran, Balaji; Ankem, Murali; Damodaran, Chendil

Published In Toxicol Appl Pharmacol, (2019 06 15)

Abstract: Earlier, we reported that chronic cadmium (Cd)-exposure to prostate epithelial (RWPE-1) cells causes defective autophagy, which leads to the transformation of a malignant phenotype in both in vitro and in vivo models. However, the upstream events responsible for defective autophagy are yet to be delineated. The present study suggests that chronic Cd exposure induces endoplasmic reticulum (ER) stress that triggers the phosphorylation of stress transducers [protein kinase R-like ER Kinase- (PERK), eukaryotic translation initiation factor 2-alpha- (eIF2-α) and Activating Transcription Factor 4 -(ATF-4)], resulting in defective autophagy that protects Cd-exposed RWPE-1 cells. On the other hand, inhibition of the ATF4 stress inducer by siRNA blocked the Cd-induced defective autophagy in transforming cells. While dissecting the upstream activators of ER stress, we found that increased expression of reactive oxygen species (ROS) is responsible for ER stress in Cd-exposed RWPE-1 cells. Overexpression of antioxidants (SOD1/SOD2) mitigates Cd-induced ROS that results in inhibition of ER stress and autophagy in prostate epithelial cells. These results suggest that the induction of ROS and subsequent ER stress are responsible for defective autophagy in Cd-induced transformation in prostate epithelial cells.

PubMed ID: 31002860 Exiting the NIEHS site

MeSH Terms: Autophagy-Related Proteins/metabolism; Autophagy/drug effects*; Cadmium/toxicity*; Cell Line, Transformed; Cell Transformation, Neoplastic/chemically induced*; Cell Transformation, Neoplastic/genetics; Cell Transformation, Neoplastic/metabolism; Cell Transformation, Neoplastic/pathology; Endoplasmic Reticulum Stress/drug effects*; Epithelial Cells/drug effects*; Epithelial Cells/metabolism; Epithelial Cells/pathology; Humans; Male; Oxidative Stress/drug effects; Phosphorylation; Prostate/drug effects*; Prostate/metabolism; Prostate/pathology; Prostatic Neoplasms/chemically induced*; Prostatic Neoplasms/genetics; Prostatic Neoplasms/metabolism; Prostatic Neoplasms/pathology; Reactive Oxygen Species/metabolism; Signal Transduction; Superoxide Dismutase-1/genetics; Superoxide Dismutase-1/metabolism; Superoxide Dismutase/genetics; Superoxide Dismutase/metabolism

to Top