Novel Anticancer Platinum(IV) Complexes with Adamantylamine: Their Efficiency and Innovative Chemotherapy Strategies Modifying Lipid Metabolism.

Alois Kozubík, Alena Vaculová, Karel Soucek, Jan Vondrácek, Jaroslav Turánek, Jirina Hofmanová
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引用次数: 15

Abstract

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.

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新型抗癌铂(IV)与金刚烷胺配合物:它们的效率和改变脂质代谢的创新化疗策略。
一方面,顺铂对癌症的影响令人印象深刻,另一方面,严重的副作用,以及治疗期间耐药性的发展,是促使科学家设计和合成新的更有效的类似物的因素,这些类似物缺乏顺铂的缺点。铂(IV)配合物是铂基药物的前景群之一。在这篇综述中,我们总结了铂(IV)配合物与金刚胺的体内和体外效应的最新发现。基于对铂基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和细胞脂质的相互作用来调节新型铂配合物作用的机会,包括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的调节。这些方法可能显著提高新型和已建立的铂基细胞抑制剂的疗效。
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