{"title":"青蒿素及其衍生物在抗癌治疗中的新研究方向青蒿素及其衍生物在抗癌治疗中的新研究方向","authors":"Youke Wang, Xiang Yuan, Min Ren, Zhiyu Wang","doi":"10.1142/S0192415X24500071","DOIUrl":null,"url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from <i>Artemisia annua L.</i>, is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects <i>in vitro</i> and <i>in vivo</i>. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"161-181"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment.\",\"authors\":\"Youke Wang, Xiang Yuan, Min Ren, Zhiyu Wang\",\"doi\":\"10.1142/S0192415X24500071\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from <i>Artemisia annua L.</i>, is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects <i>in vitro</i> and <i>in vivo</i>. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.</p>\",\"PeriodicalId\":94221,\"journal\":{\"name\":\"The American journal of Chinese medicine\",\"volume\":\" \",\"pages\":\"161-181\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The American journal of Chinese medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1142/S0192415X24500071\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The American journal of Chinese medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1142/S0192415X24500071","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/7 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
铁中毒是一种由细胞膜上脂质过氧化物积累驱动的铁依赖性细胞死亡机制,已成为治疗包括癌症在内的各种疾病的一种有前途的策略。铁氧化诱导剂不仅对多种癌细胞(包括耐药性癌症变种)具有细胞毒性作用,而且还具有作为辅助药物提高免疫疗法等其他抗癌疗法疗效的潜力。除合成诱导剂外,青蒿素等天然化合物也可被视为铁突变诱导剂。青蒿素提取自黄花蒿,是一种水溶性很差的抗疟药物。为了临床应用,研究人员合成了各种水溶性青蒿素衍生物,如双氢青蒿素、青蒿琥酯和蒿甲醚。青蒿素和青蒿素衍生物(ARTEs)可上调细胞内游离铁水平,促进细胞内脂质过氧化物的积累,从而诱导癌细胞铁变态反应,缓解癌症的发展,在体外和体内产生强大的抗癌作用。在这篇综述中,我们介绍了铁突变的机制,总结了 ARTEs 诱导癌细胞铁突变的研究,并讨论了 ARTEs 在抗癌治疗中的临床研究进展和目前面临的挑战。这篇综述加深了目前人们对 ARTEs 与铁突变之间关系的理解,并为 ARTEs 未来的临床抗癌应用提供了理论依据。
Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment.
Ferroptosis, an iron-dependent cell death mechanism driven by an accumulation of lipid peroxides on cellular membranes, has emerged as a promising strategy to treat various diseases, including cancer. Ferroptosis inducers not only exhibit cytotoxic effects on multiple cancer cells, including drug-resistant cancer variants, but also hold potential as adjuncts to enhance the efficacy of other anti-cancer therapies, such as immunotherapy. In addition to synthetic inducers, natural compounds, such as artemisinin, can be considered ferroptosis inducers. Artemisinin, extracted from Artemisia annua L., is a poorly water-soluble antimalarial drug. For clinical applications, researchers have synthesized various water-soluble artemisinin derivatives such as dihydroartemisinin, artesunate, and artemether. Artemisinin and artemisinin derivatives (ARTEs) upregulate intracellular free iron levels and promote the accumulation of intracellular lipid peroxides to induce cancer cell ferroptosis, alleviating cancer development and resulting in strong anti-cancer effects in vitro and in vivo. In this review, we introduce the mechanisms of ferroptosis, summarize the research on ARTEs-induced ferroptosis in cancer cells, and discuss the clinical research progress and current challenges of ARTEs in anti-cancer treatment. This review deepens the current understanding of the relationship between ARTEs and ferroptosis and provides a theoretical basis for the clinical anti-cancer application of ARTEs in the future.