Trabectedin (ET-743) in prostate cancer: Endoplasmic reticulum stress-induced apoptotic effect

ATMACA İLHAN H., Oğuz F., İLHAN M. S.

Andrologia, cilt.54, sa.11, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 54 Sayı: 11
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1111/and.14599
  • Dergi Adı: Andrologia
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Gender Studies Database, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: apoptosis, cytotoxicity, ER stress, oxidative stress, prostate cancer, trabectedin
  • Manisa Celal Bayar Üniversitesi Adresli: Evet

Özet

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.