Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun 130103, China.
Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun 130103, China.
Biomed Pharmacother. 2024 Sep;178:117214. doi: 10.1016/j.biopha.2024.117214. Epub 2024 Jul 29.
Apoptosis signal-regulated kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase (MAP3K) family, whose activation and regulation are intricately associated with apoptosis. ASK1 is activated in response to oxidative stress, among other stimuli, subsequently triggering downstream JNK, p38 MAPK, and mitochondria-dependent apoptotic signaling, which participate in the initiation of tumor cell apoptosis induced by various stimuli. Research has shown that ASK1 plays a crucial role in the apoptosis of lung cancer, breast cancer, and liver cancer cells. Currently, the investigation of effective ASK1 activators is a hot topic in research on tumor cell apoptosis. Synthetic compounds such as human β-defensin, triazolothiazide derivatives and heat shock protein 27 inhibitors; natural compounds such as quercetin, Laminarina japonica polysaccharide-1 peptide and theabrownin; and nanomedicines such as cerium oxide nanoparticles, magnetite FeO nanoparticles and silver nanoparticles can activate ASK1 and induce apoptosis in various tumor cells. This review extensively investigates the roles and activation mechanisms of ASK1, explores its impact on a variety of apoptotic signaling pathways, and discusses the potential therapeutic applications of various ASK1 activators in cancer treatment. In addition, this paper provides an in-depth discussion of the future development of this field and proposes a promising method for further research and clinical progress.
凋亡信号调节激酶 1（ASK1）是丝裂原活化蛋白激酶激酶（MAP3K）家族的成员，其激活和调节与细胞凋亡密切相关。ASK1 被激活的原因有很多，包括氧化应激等刺激因素，随后触发下游 JNK、p38 MAPK 和线粒体依赖性凋亡信号通路，参与各种刺激诱导的肿瘤细胞凋亡的启动。研究表明，ASK1 在肺癌、乳腺癌和肝癌细胞凋亡中起着关键作用。目前，寻找有效的 ASK1 激活剂是研究肿瘤细胞凋亡的热点。合成化合物，如人β-防御素、三唑并噻二嗪衍生物和热休克蛋白 27 抑制剂；天然化合物，如槲皮素、昆布多糖-1 肽和茶棕素；以及纳米药物，如氧化铈纳米颗粒、磁铁矿 FeO 纳米颗粒和银纳米颗粒等，都可以激活 ASK1，诱导各种肿瘤细胞凋亡。本综述广泛研究了 ASK1 的作用和激活机制，探讨了其对多种凋亡信号通路的影响，并讨论了各种 ASK1 激活剂在癌症治疗中的潜在治疗应用。此外，本文还深入讨论了该领域的未来发展，并提出了一种有前途的方法，以进一步研究和临床进展。
