Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Victoria, 3086, Australia.
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.
Med Res Rev. 2016 Mar;36(2):248-99. doi: 10.1002/med.21364. Epub 2015 Aug 19.
Mitoxantrone is a synthetic anthracenedione originally developed to improve the therapeutic profile of the anthracyclines and is commonly applied in the treatment of breast and prostate cancers, lymphomas, and leukemias. A comprehensive overview of the drug's molecular, biochemical, and cellular pharmacology is presented here, beginning with the cardiotoxic nature of its predecessor doxorubicin and how these properties shaped the pharmacology of mitoxantrone itself. Although mitoxantrone is firmly established as a DNA topoisomerase II poison within mammalian cells, it is now clear that the drug interacts with a much broader range of biological macromolecules both covalently and noncovalently. Here, we consider each of these interactions in the context of their wider biological relevance to cancer therapy and highlight how they may be exploited to further enhance the therapeutic value of mitoxantrone. In doing so, it is now clear that mitoxantrone is more than just another topoisomerase II poison.
米托蒽醌是一种合成蒽二酮，最初是为了改善蒽环类药物的治疗效果而开发的，常用于治疗乳腺癌、前列腺癌、淋巴瘤和白血病。本文全面概述了该药物的分子、生化和细胞药理学，从其前体阿霉素的心脏毒性性质以及这些性质如何影响米托蒽醌本身的药理学开始。尽管米托蒽醌已被确定为哺乳动物细胞中的 DNA 拓扑异构酶 II 毒物，但现在很清楚，该药物与更广泛的生物大分子发生共价和非共价相互作用。在这里，我们根据它们与癌症治疗的更广泛生物学相关性来考虑这些相互作用，并强调如何利用这些相互作用进一步提高米托蒽醌的治疗价值。这样做的同时，现在很清楚的是，米托蒽醌不仅仅是另一种拓扑异构酶 II 毒物。
