Neuzil Jiri, Dong Lan-Feng, Ramanathapuram Lalitha, Hahn Tobias, Chladova Miroslava, Wang Xiu-Fang, Zobalova Renata, Prochazka Lubomir, Gold Mikhal, Freeman Ruth, Turanek Jaroslav, Akporiaye Emmanuel T, Dyason Jeffrey C, Ralph Stephen J
Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Qld, Australia.
Mol Aspects Med. 2007 Oct-Dec;28(5-6):607-45. doi: 10.1016/j.mam.2007.02.003. Epub 2007 Feb 23.
Mitochondria have recently emerged as new and promising targets for cancer prevention and therapy. One of the reasons for this is that mitochondria are instrumental to many types of cell death and often lie downstream from the initial actions of anti-cancer drugs. Unlike the tumour suppressor gene encoding p53 that is notoriously prone to inactivating mutations but whose function is essential for induction of apoptosis by DNA-targeting agents (such as doxorubicin or 5-fluorouracil), mitochondria present targets that are not so compromised by genetic mutation and whose targeting overcomes problems with mutations of upstream targets such as p53. We have recently proposed a novel class of anti-cancer agents, mitocans that exert their anti-cancer activity by destabilising mitochondria, promoting the selective induction of apoptotic death in tumour cells. In this communication, we review recent findings on mitocans and propose a common basis for their mode of action in inducing apoptosis of cancer cells. We use as an example the analogues of vitamin E that are proving to be cancer cell-specific and may soon be developed into efficient anti-cancer drugs.
线粒体最近已成为癌症预防和治疗新的、有前景的靶点。原因之一是线粒体对多种类型的细胞死亡至关重要，且常常处于抗癌药物初始作用的下游。与编码p53的肿瘤抑制基因不同，p53极易发生失活突变，但其功能对于DNA靶向药物（如阿霉素或5-氟尿嘧啶）诱导凋亡至关重要，线粒体所呈现的靶点不会因基因突变而严重受损，靶向线粒体可克服诸如p53等上游靶点突变带来的问题。我们最近提出了一类新型抗癌药物——线粒体靶向化合物（mitocans），它们通过破坏线粒体的稳定性发挥抗癌活性，促进肿瘤细胞中凋亡性死亡的选择性诱导。在本通讯中，我们综述了关于线粒体靶向化合物的最新研究结果，并提出了它们诱导癌细胞凋亡作用模式的共同基础。我们以维生素E类似物为例，事实证明这些类似物具有癌细胞特异性，可能很快会被开发成有效的抗癌药物。
