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

Author(s):

ZhengPing Wu, MengQiao Su, HanWu Chen, XuZhou Chen, Chung-Yi Chen, LiJie An, ZiChen Shao, XiaoYu Liu, Yi Lin, Ai-Jun OuYang and Chi-Ming Liu*   Pages 1457 - 1468 ( 12 )

Abstract:

<p> 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. </p><p> Aim: The aim of the study is to examine the anticancer effects of sinularin in prostate cancer cells. </p><p> 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. </p><p> 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 5&#945;-reductase, and prostate-specific antigen (PSA). Sinularin significantly attenuated the invasion and migration ability of PC3 and DU145 cells, with or without TGF-&#946;1 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. </p><p> 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.</p>

Keywords:

Sinularin, epithelial-mesenchymal transition (EMT), apoptosis, autophagy, ferroptosis, prostate cancer.

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