Work

Repurposing antidepressant sertraline as a pharmacological drug to target prostate cancer stem cells: dual activation of apoptosis and autophagy signaling by deregulating redox balance.

Year: 2020

Type: article

Abstract: ), lipid peroxidation (LPO) and depleted the levels of glutathione (GSH). Moreover, surface marker expression analysis using confocal revealed that STL significantly down regulates the expression levels of aldehyde dehydrogenase 1 (ALDH1) and cluster of differentiation 44 (CD44) stem cell markers. Furthermore, in western blot analysis, STL treatment applied in a dose-dependent manner, caused a marked decrease in TCTP, phospho TCTP, anti-apoptotic markers survivin and cellular inhibitor of apoptosis protein 1 (cIAP1) expression as well as a significant increase in cleaved caspase3 and cleaved Poly [ADP-ribose] polymerase 1 (PARP-1) expression. Of note, STL also significantly down regulated the stem cell markers (ALDH1 and CD44) and epithelial to mesenchymal transition (EMT) markers such as transcription factor 8 (TCF8) and lymphoid enhancer-binding factor-1 (LEF1) expression levels. Concurrently, STL increased the levels of autophagy markers such as light chain (LC3), Beclin1 and autophagy-related gene (ATG5). Taken together, our study suggests that STL could be an effective therapeutic agent in eliminating prostate cancer stem cells.

Source: PubMed Central

Authors: Somaiah Chinnapaka, Velavan Bakthavachalam, Gnanasekar Munirathinam

Institution: University of Illinois Chicago, Rockford campus

Language: English

Topic: Prostate Cancer Treatment and Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute

Award: Targeting TCTP Signaling to Control Castration-Resistant Prostate Cancer