CNR Institute of Neuroscience and Dept. of Experimental Biomedical Sciences, University of Padova, Padova, Italy.
Mitochondrion. 2010 Nov;10(6):670-81. doi: 10.1016/j.mito.2010.06.004. Epub 2010 Jul 1.
Cancer is an ever-increasing problem that is yet to be harnessed. Frequent mutations make this pathology very variable and, consequently, a considerable challenge. Intriguingly, mitochondria have recently emerged as novel targets for cancer therapy. A group of agents with anti-cancer activity that induce apoptosis by way of mitochondrial destabilisation, termed mitocans, have been a recent focus of research. Of these compounds, many are hydrophobic agents that associate with various sub-cellular organelles. Clearly, modification of such structures with mitochondria-targeting moieties, for example tagging them with lipophilic cations, would be expected to enhance their activity. This may be accomplished by the addition of triphenylphosphonium groups that direct such compounds to mitochondria, enhancing their activity. In this paper, we will review agents that possess anti-cancer activity by way of destabilizing mitochondria and their possible targets. We propose that mitochondrial targeting, in particular where the agent associates directly with the target, results in more specific and efficient anti-cancer drugs of potential high clinical relevance.
癌症是一个日益严重的问题，尚未得到有效控制。频繁的突变使这种病理学非常多变，因此是一个相当大的挑战。有趣的是，线粒体最近成为癌症治疗的新靶点。一组具有抗癌活性的药物通过线粒体去稳定化诱导细胞凋亡，称为线粒体靶向药物，是最近研究的重点。在这些化合物中，许多是与各种亚细胞细胞器结合的疏水性药物。显然，用线粒体靶向部分修饰这些结构，例如用脂溶性阳离子对其进行标记，有望提高它们的活性。这可以通过添加三苯基膦基团来实现，该基团将此类化合物导向线粒体，从而增强其活性。在本文中，我们将综述通过破坏线粒体来发挥抗癌活性的药物及其可能的靶点。我们提出，线粒体靶向，特别是药物直接与靶标结合，会产生更具特异性和更有效的抗癌药物，具有潜在的高临床相关性。
