%0 Journal Article
%T Effects of Cisplatin in Neuroblastoma Rat Cells: Damage to Cellular Organelles
%A Giada Santin
%A Luigi Scietti
%A Paola Veneroni
%A Sergio Barni
%A Graziella Bernocchi
%A Maria Grazia Bottone
%J International Journal of Cell Biology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/424072
%X Cisplatin (cisPt) is a chemotherapy agent used as a treatment for several types of cancer. The main cytotoxic effect of cisplatin is generally accepted to be DNA damage. Recently, the mechanism by which cisPt generates the cascade of events involved in the apoptotic process has been demonstrated. In particular it has been shown that some organelles are cisPt target and are involved in cell death. This paper aims to describe the morphological and functional changes of the Golgi apparatus and lysosomes during apoptosis induced in neuronal rat cells (B50) by cisplatin. The results obtained show that the cellular organelles are the target of cisPt, so their damage can induce cell death. 1. Introduction From many years, cisplatin (cisPt) was used in chemotherapy of different cancers because of its apoptotic effects. It binds DNA-generating adduct cisPt/DNA that provokes the distortion of double helix blocking the transcription and the replication processes [1]. We reported that, in B50 neuroblastoma rat cells, cisPt induces cytotoxic cell death mediated by activation of death receptor-mediated apoptotic signaling mechanisms as well as mitochondrial pathways [2, 3]. Nevertheless, organelles damage cisPt induced is today not so well elucidated. The cytotoxic action of this drug can be initiated by cytoplasmic events thus determining organelle damage. Yu et al. [4] demonstrated, in fact, that cisplatin initiates apoptosis from the cytoplasm and suggested that nuclear events may not be critical for the initiation of cisplatin-induced cytotoxicity, at least, not in immortalized mouse kidney proximal tubule epithelial (TKPTS) cells [4]. Apoptosis is a genetically controlled cell death program consisting of several essential steps that are critical checkpoints, as well as nonessential steps depending on the cell type, context, or pathophysiological stimuli [5]. Moreover, the intricate network of relationships and communication (i.e., crosstalk in which multiple organelles emit signals and receive responses) occurs between all the cellular organelles. During apoptosis, the cytoskeleton undergoes disassembly, bringing with him the different organelles, such as the Golgi vesicles, which in apoptosis following the reorganization of microtubules [6¨C8] wasting a clear spatial organization in the cell [9, 10]. Mitochondria and endoplasmic reticulum are, respectively, involved in intrinsic apoptotic pathway and in the pathway mediated by caspase 12 [11]. We have demonstrated that in B50 neuronal rat cells cisplatin induces apoptosis, morphological and functional
%U http://www.hindawi.com/journals/ijcb/2012/424072/