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Sinularin Exerts Anti-cancer Effects by Inducing Oxidative Stress-mediated Ferroptosis, Apoptosis, and Autophagy in
ZhengPing Wu1, MengQiao Su2,3, HanWu Chen2
1School of Aesthetic Medicine, Yichun University, 576 XueFu Road, Yuanzhou District, Yichun, 336000, Jiangxi Province, China.
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.
Insights
Sinularin, a natural compound, effectively inhibits prostate cancer cell growth and triggers cell death pathways. Further research is needed to explore its potential as a therapeutic agent for prostate cancer.
Area of Science:
- Marine natural products chemistry
- Cancer biology
- Pharmacology
Background:
- Prostate cancer is a leading cause of cancer-related death in men.
- Sinularin, a compound from soft corals, exhibits anticancer properties in various cancer cells.
- The specific mechanisms of sinularin's action in prostate cancer remain largely uncharacterized.
Purpose of the Study:
- To investigate the anticancer effects of sinularin on human prostate cancer cell lines.
- To elucidate the molecular mechanisms underlying sinularin's anti-prostate cancer activity.
Main Methods:
- Utilized MTT assays, Transwell assays, and wound healing assays to assess cell viability, invasion, and migration.
- Employed flow cytometry and western blotting to analyze apoptosis, autophagy, ferroptosis, and key protein expression.
- Examined effects on androgen receptor (AR) signaling, epithelial-mesenchymal transition (EMT), and oxidative stress markers.
Main Results:
- Sinularin significantly reduced prostate cancer cell viability and colony formation.
- It suppressed testosterone-induced growth in LNCaP cells by downregulating AR, 5α-reductase, and PSA.
- Sinularin inhibited cell invasion, migration, and EMT, while inducing apoptosis, autophagy, and ferroptosis through modulation of specific proteins and reactive oxygen species (ROS).
Conclusions:
- Sinularin demonstrates potent anticancer effects against prostate cancer cells by targeting the AR signaling pathway and inducing multiple cell death modalities.
- These findings suggest sinularin holds promise as a potential therapeutic candidate for prostate cancer, warranting further clinical investigation.
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