Kozubík Alois, Vaculová Alena, Soucek Karel, Vondrácek Jan, Turánek Jaroslav, Hofmanová Jirina
Department of Cytokinetics, Institute of Biophysics, Královopolská 135, 612 65 Brno, Czech Republic.
Met Based Drugs. 2008;2008:417897. doi: 10.1155/2008/417897.
The impressive impact of cisplatin on cancer on one side and severe side effects, as well as the development of drug resistance during treatment on the other side, were the factors motivating scientists to design and synthesize new more potent analogues lacking disadvantages of cisplatin. Platinum(IV) complexes represent one of the perspective groups of platinum-based drugs. In this review, we summarize recent findings on both in vitro and in vivo effects of platinum(IV) complexes with adamantylamine. Based on a literary overview of the mechanisms of activity of platinum-based cytostatics, we discuss opportunities for modulating the effects of novel platinum complexes through interactions with apoptotic signaling pathways and with cellular lipids, including modulations of the mitochondrial cell death pathway, oxidative stress, signaling of death ligands, lipid metabolism/signaling, or intercellular communication. These approaches might significantly enhance the efficacy of both novel and established platinum-based cytostatics.
顺铂一方面对癌症有着显著疗效,另一方面却有严重的副作用,且在治疗过程中会产生耐药性,这些因素促使科学家设计并合成新的、更有效的类似物,以克服顺铂的缺点。铂(IV)配合物是铂类药物中有前景的一类。在本综述中,我们总结了近期关于含金刚烷胺的铂(IV)配合物的体外和体内效应的研究结果。基于对铂类细胞抑制剂活性机制的文献综述,我们讨论了通过与凋亡信号通路以及细胞脂质相互作用来调节新型铂配合物效应的机会,包括调节线粒体细胞死亡途径、氧化应激、死亡配体信号传导、脂质代谢/信号传导或细胞间通讯。这些方法可能会显著提高新型和已有的铂类细胞抑制剂的疗效。