Trabectedin (ET-743) in prostate cancer: Endoplasmic reticulum stress-induced apoptotic effect
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Date
2022
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Abstract
Trabectedin is a chemotherapy agent originating from a tunicate, Ecteinascidia turbinata. In this study, DNA-independent action mechanisms of trabectedin are investigated in prostate cancer (PCa) cells. Cell viability was assessed via XTT assay. Apoptosis was evaluated via flow cytometry. Tetramethylrodamine ethyl ester (TMRE) dye was utilized to determine mitochondrial membrane potential (MMP). Cell cycle distribution was investigated via flow cytometric analysis. Reactive oxygen species (ROS) were monitored using fluorescence CM-H2DCFDA dye. Changes in CHOP, p-eIF2α, GRP78 and p-PERK which are endoplasmic reticulum (ER) stress-involved proteins were investigated via western blot. Trabectedin induced cytotoxicity and cell cycle arrest at the G2/M phase. Trabectedin decreased MMP via ROS generation in PCa cells. ER stress-related proteins CHOP, p-eIF2α, GRP78 and p-PERK were also elevated by trabectedin treatment indicating the induction of ER stress-induced apoptosis. The results of this study show that trabectedin may be an effective chemotherapeutic for PCa. © 2022 Wiley-VCH GmbH.
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Keywords
Apoptosis , Cell Line, Tumor , Endoplasmic Reticulum Stress , Humans , Male , Prostatic Neoplasms , Reactive Oxygen Species , Trabectedin , endoplasmic reticulum chaperone BiP , fluorescent dye , growth arrest and DNA damage inducible protein 153 , initiation factor 2alpha , matrix metalloproteinase , mitogen activated protein kinase , reactive oxygen metabolite , tetramethylrodamine ethyl ester , trabectedin , unclassified drug , reactive oxygen metabolite , trabectedin , apoptosis , apoptotic cell percentage , Article , cancer inhibition , cell cycle arrest , cell cycle G1 phase , cell viability , drug mechanism , DU145 cell line , endoplasmic reticulum stress , flow cytometry , G2 phase cell cycle checkpoint , HEK293 cell line , human , human cell , IC50 , mitochondrial membrane potential , oxidative stress , PC-3 [Human prostate carcinoma] cell line , prostate cancer , protein expression , Western blotting , XTT assay , apoptosis , male , metabolism , prostate tumor , tumor cell line