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


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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.

About the authors

ZhengPing Wu

School of Aesthetic Medicine, Yichun University

Email: info@benthamscience.net

MengQiao Su

School of Medicine,, Yichun University,

Email: info@benthamscience.net

HanWu Chen

School of Medicine, Yichun University

Email: info@benthamscience.net

XuZhou Chen

School of Medicine, Yichun University

Email: info@benthamscience.net

Chung-Yi Chen

School of Medical and Health Sciences, Fooyin University

Email: info@benthamscience.net

LiJie An

School of Medicine, Yichun University

Email: info@benthamscience.net

ZiChen Shao

College of Chemistry and Bio-engineering, Yichun University

Email: info@benthamscience.net

XiaoYu Liu

School of Aesthetic Medicine, Yichun University

Email: info@benthamscience.net

Yi Lin

School of Aesthetic Medicine, Yichun University

Email: info@benthamscience.net

Ai-Jun OuYang

Department of Pharmacy, First Affiliated Hospital of Nanchang University

Email: info@benthamscience.net

Chi-Ming Liu

School of Medicine, Yichun University

Author for correspondence.
Email: info@benthamscience.net

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