Bicalutamide elicits renal damage by causing mitochondrial dysfunction via ROS damage and upregulation of HIF-1α

Kuan Chou Chen, Chang Rong Chen, Chang Yu Chen, Kai Yi Tzou, Chiung Chi Peng, Robert Y. Peng

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Combined androgen blockade using bicalutamide (Bic) is a therapeutic choice for treating prostate cancer (PCa). However, even at regular clinical dosages, Bic frequently shows adverse effects associated with cardiovascular and renal damage. Previously, we found that Bic selectively damaged mesangial cells compared to tubular cells and in an in vivo rat model, we also found renal damage caused by Bic. In the present study, a rat mesangial cell model was used to further the investigation. Results indicated that Bic enhanced lactate dehydrogenase release, reactive oxygen species (ROS) production, lysosome population and kidney injury molecule-1 and decreased N-cadherin. Bic elicited mitochondrial swelling and reduced the mitochondrial potential, resulting in severe suppression of the oxygen consumption rate (OCR), maximum respiration and ATP production. The hypoxia-inducible factor (HIF)-1α transcriptional activity and messenger RNA were significantly upregulated in dose-dependent manners. The HIF-1α protein reached a peak value at 24 h then rapidly decayed. BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 and cleaved caspase-3 were dose-dependently upregulated by Bic (60 μM) and that eventually led to cell apoptosis. It is suggested that Bic induces renal damage via ROS and modulates HIF-1α pathway and clinically, some protective agents like antioxidants are recommended for co-treatment.

Original languageEnglish
Article number3400
JournalInternational journal of molecular sciences
Volume21
Issue number9
DOIs
Publication statusPublished - May 1 2020

Keywords

  • Bicalutamide (Bic)
  • HIF-1α
  • Mitochondrial dysfunction
  • Oxygen consumption rate (OCR)
  • Rat mesangial cell (RMC) line

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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