Sinularin Exerts Anti-cancer Effects by Inducing Oxidative Stress-mediated Ferroptosis, Apoptosis, and Autophagy in Prostate Cancer Cells

Anticancer Agents Med Chem. 2023;23(12):1457-1468. doi: 10.2174/1871520623666230331083744.

Abstract

Introduction: Prostate cancer is the second-leading cause of cancer death in men. Sinularin is a soft coralsderived natural compound that has anticancer activity in many cancer cells. However, the pharmacological action of sinularin in prostate cancer is unclear.

Aim: The aim of the study is to examine the anticancer effects of sinularin in prostate cancer cells.

Methods: We explored the anticancer effects of sinularin on the prostate cancer cell lines, PC3, DU145, and LNCaP, by MTT, Transwell assay, wound healing, flow cytometry, and western blotting.

Results: Sinularin inhibited the cell viability and colony formation of these cancer cells. Furthermore, sinularin inhibited testosterone-induced cell growth in LNCaP cells by downregulating the protein expression levels of androgen receptor (AR), type Ⅱ 5α-reductase, and prostate-specific antigen (PSA). Sinularin significantly attenuated the invasion and migration ability of PC3 and DU145 cells, with or without TGF-β1 treatment. Sinularin inhibited epithelialmesenchymal transition (EMT) in DU145 cells after 48 h of treatment by regulating the protein expression levels of Ecadherin, N-cadherin, and vimentin. Sinularin induced apoptosis, autophagy, and ferroptosis by regulating the protein expression levels of Beclin-1, LC3B, NRF2, GPX4, PARP, caspase-3, caspase-7, caspase-9, cleaved-PARP, Bcl-2, and Bax. Moreover, intracellular reactive oxygen species (ROS) were increased but glutathione was decreased after sinularin treatment in PC3, DU145 and LNCaP cells.

Conclusion: Sinularin regulated the androgen receptor signaling pathway and triggered apoptosis, autophagy, and ferroptosis in prostate cancer cells. In conclusion, the results indicated that sinularin may be a candidate agent for human prostate cancer and need further study for being applied to human.

Keywords: Sinularin; apoptosis; autophagy; epithelial-mesenchymal transition (EMT); ferroptosis; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Autophagy
  • Cell Line, Tumor
  • Cell Proliferation
  • Ferroptosis*
  • Humans
  • Male
  • Oxidative Stress
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / metabolism
  • Receptors, Androgen / metabolism

Substances

  • Receptors, Androgen
  • sinularin
  • Poly(ADP-ribose) Polymerase Inhibitors