Wu Yimao, Chen Xiaoyan, Chen Zichang, Ma Yunqi
School of Pharmacy, Binzhou Medical University, Yantai 264003, China.
Second Clinical Medical College, Guangdong Medical University, Dongguan 523808, China.
Mar Drugs. 2025 Jun 19;23(6):258. doi: 10.3390/md23060258.
This article reviews the mechanisms by which marine natural products regulate ferroptosis and their potential applications in tumor therapy. Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation, characterized primarily by the accumulation of lipid peroxides and the failure of antioxidant defense systems. Due to their unique chemical structural diversity, marine natural products demonstrate significant advantages in regulating the ferroptosis pathway. Studies showed that marine compounds target key molecules such as glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthetase 4 (ACSL4(a)) ACSL4(1) to modulate lipid peroxidation and iron metabolism, inducing ferroptosis in tumor cells and reshaping the tumor microenvironment (TME). In addition, marine compounds can enhance anti-tumor effects by activating immune responses. Although marine compounds hold great potential in regulating ferroptosis, their clinical translation faces challenges such as low bioavailability and tumor type dependency. Future research needs to integrate multi-omics techniques to further analyze the mechanisms of marine compounds and develop precision therapeutic strategies based on marine compounds to overcome the bottlenecks in ferroptosis therapy.
本文综述了海洋天然产物调节铁死亡的机制及其在肿瘤治疗中的潜在应用。铁死亡是一种由铁依赖性脂质过氧化驱动的程序性细胞死亡形式，主要特征是脂质过氧化物的积累和抗氧化防御系统的失效。由于其独特的化学结构多样性，海洋天然产物在调节铁死亡途径方面具有显著优势。研究表明，海洋化合物靶向谷胱甘肽过氧化物酶4（GPX4）和长链酰基辅酶A合成酶4（ACSL4(a)）、ACSL4(1)等关键分子，调节脂质过氧化和铁代谢，诱导肿瘤细胞铁死亡并重塑肿瘤微环境（TME）。此外，海洋化合物可通过激活免疫反应增强抗肿瘤作用。尽管海洋化合物在调节铁死亡方面具有巨大潜力，但其临床转化面临生物利用度低和肿瘤类型依赖性等挑战。未来的研究需要整合多组学技术，进一步分析海洋化合物的作用机制，并基于海洋化合物开发精准治疗策略，以克服铁死亡治疗中的瓶颈。
