Unfolded Protein Response is Involved in Trans-Platinum (II) Complex-Induced Apoptosis in Prostate Cancer Cells via

Didem Karakas1,2, Buse Cevatemre2,3, Arzu Y Oral4

  • 1Department of Molecular Biology and Genetics, Faculty of Science and Letters, Istinye University, Istanbul, Turkey.

Abstract

Insights

A new Platinum (II) complex shows significant anti-cancer activity against prostate cancer cells. This compound induces cell death through ROS-mediated endoplasmic reticulum stress and apoptosis, suggesting its potential as a novel drug candidate.

Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Cell Biology

Background:

  • Prostate cancer is a leading cause of cancer death in men globally.
  • Existing treatments have limitations, necessitating the development of novel therapeutic compounds.
  • Novel platinum (II) complexes are being investigated for their anti-cancer potential.

Purpose of the Study:

  • To evaluate the anti-cancer activity of a newly synthesized Platinum (II) [Pt(II)] complex.
  • To assess the cytotoxic effects and cell death mechanisms of the Pt(II) complex on prostate cancer cell lines.
  • To investigate the role of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress in Pt(II) complex-induced cell death.

Main Methods:

  • Synthesis and characterization of a novel Platinum (II) complex.
  • In vitro evaluation of cytotoxic activity using SRB and ATP cell viability assays on DU145, LNCaP, and PC-3 prostate cancer cell lines.
  • Analysis of apoptosis induction via fluorescent staining, flow cytometry, and western blot, including assessment of mitochondrial membrane potential and ROS generation.

Main Results:

  • The Pt(II) complex significantly reduced cell viability in a dose-dependent manner across tested prostate cancer cell lines.
  • Apoptotic markers and DNA damage were elevated, particularly in PC-3 cells, indicating sensitivity to the Pt(II) complex.
  • Pt(II) complex induced ER stress and ROS generation, which were alleviated by N-acetylcysteine (NAC), suggesting a role in cell death.

Conclusions:

  • The Pt(II) complex induces prostate cancer cell death via ROS-mediated ER stress and apoptosis.
  • ROS production plays an upstream role in the Pt(II) complex-induced apoptotic pathway.
  • This Pt(II) complex demonstrates potential as a novel metal-containing anti-cancer drug candidate for prostate cancer treatment.

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