顺铂
亚细胞定位
细胞器
内质网
胞浆
细胞生物学
线粒体
细胞骨架
程序性细胞死亡
细胞
细胞毒性
生物
细胞凋亡
生物化学
体外
细胞质
酶
化疗
遗传学
作者
Sandra M. Sancho-Martínez,Laura Prieto-García,María Isabel Prieto Barrio,José M. López‐Novoa,Francisco J. López‐Hernández
标识
DOI:10.1016/j.pharmthera.2012.07.003
摘要
Cisplatin is a chemotherapeutic drug widely used against a variety of cancers. Its clinical utility is severely limited by its toxicity, which mainly affects, but is not limited to, the inner ear and renal tubules. Cisplatin toxicity is determined by target tissue and cell accumulation, subcellular handling and trafficking through diverse subcellular structures, and interaction with macromolecules. Cisplatin accumulates and stresses different organelles from which delay signaling is activated, including mitochondria, lysosomes, the endoplasmic reticulum, the nucleus, the cell membrane and cytoskeleton, and can also be found in the cytosol. This article critically summarizes the available information in order to establish the connection among its known subcellular effects in a hierarchical and integrative framework. Cisplatin causes different types of cell death in a concentration-dependent manner. Knowledge of the events and signaling leading to the different phenotypes is also intertwined within the model, within the scope of the potential utility of this information in the improvement of the pharmacotoxicological profile of this drug. Perspectives for the key aspects that need to be addressed by future investigation are also outlined.
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