Institute for Molecular Medicine I, Medical Faculty, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Institute of Pharmaceutical Biology and Biotechnology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Bioorg Med Chem. 2019 Oct 15;27(20):115042. doi: 10.1016/j.bmc.2019.115042. Epub 2019 Aug 8.
In order to overcome therapy resistance in cancer, scientists search in nature for novel lead structures for the development of improved chemotherapeutics. Anthraquinones belong to a class of tricyclic organic natural compounds with promising anti-cancer effects. Anthraquinone derivatives are rich in structural diversity, and exhibit pleiotropic properties, among which the modulation of autophagy seems promising in the context of overcoming cancer-therapy resistance. Among the most promising derivatives in this regard are emodin, aloe emodin, rhein, physcion, chrysophanol and altersolanol A. On the molecular level, these compounds target autophagy via different upstream pathways including the AKT/mTOR-axis and transcription of autophagy-related proteins. The role of autophagy is pro-survival as well as cell death-promoting, depending on derivatives and their cell type specificity. This review summarizes observed effects of anthraquinone derivatives on autophagy and discusses targeted pathways and crosstalks. A cumulative knowledge about this topic paves the way for further research on modes of action, and aids to find a therapeutic window of anthraquinones in cancer-therapy.
为了克服癌症的治疗抵抗，科学家们在自然界中寻找新型的先导结构，以开发改良的化疗药物。蒽醌类化合物属于具有有希望的抗癌作用的三环类有机天然化合物。蒽醌衍生物在结构多样性上非常丰富，并表现出多种性质，其中自噬的调节在克服癌症治疗抵抗方面似乎很有前景。在这方面最有前途的衍生物包括大黄素、芦荟大黄素、大黄酸、大黄素、大黄酚和 alternariol A。在分子水平上，这些化合物通过不同的上游途径靶向自噬，包括 AKT/mTOR 轴和自噬相关蛋白的转录。自噬的作用是促进生存和促进细胞死亡，这取决于衍生物及其细胞类型特异性。这篇综述总结了蒽醌衍生物对自噬的观察到的影响，并讨论了靶向途径和串扰。关于这个主题的综合知识为进一步研究作用模式铺平了道路，并有助于在癌症治疗中找到蒽醌类化合物的治疗窗。
