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Effects of Cisplatin in Neuroblastoma Rat Cells: Damage to Cellular Organelles

DOI: 10.1155/2012/424072

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Abstract:

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 [6–8] 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

References

[1]  R. C. Todd and S. J. Lippard, “Inhibition of transcription by platinum antitumor compounds,” Metallomics, vol. 1, no. 4, pp. 280–291, 2009.
[2]  G. Santin, V. M. Piccolini, P. Veneroni, S. Barni, G. Bernocchi, and M. G. Bottone, “Different patterns of apoptosis in response to cisplatin in B50 neuroblastoma rat cells,” Histology and Histopathology, vol. 26, no. 7, pp. 831–842, 2011.
[3]  G. Bernocchi, M. G. Bottone, V. M. Piccolini, et al., “Developing central nervous system and vulnerability to platinum compounds,” Chemotherapy Research and Practice, vol. 2011, Article ID 315418, 14 pages, 2011.
[4]  F. Yu, J. Megyesi, and P. M. Price, “Cytoplasmic initiation of cisplatin cytotoxicity,” American Journal of Physiology, vol. 295, no. 1, pp. F44–F52, 2008.
[5]  M. Le Bras, I. Rouy, and C. Brenner, “The modulation of inter-organelle cross-talk to control apoptosis,” Medicinal Chemistry, vol. 2, no. 1, pp. 1–12, 2006.
[6]  T. Nakagawa and J. Yuan, “Cross-talk between two cysteine protease families: activation of caspase-12 by calpain in apoptosis,” Journal of Cell Biology, vol. 150, no. 4, pp. 887–894, 2000.
[7]  J. D. Lane, J. Lucocq, J. Pryde et al., “Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis,” Journal of Cell Biology, vol. 156, no. 3, pp. 495–509, 2002.
[8]  R. Chiu, L. Novikov, S. Mukherjee, and D. Shields, “A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis,” Journal of Cell Biology, vol. 159, no. 4, pp. 637–648, 2002.
[9]  C. Soldani, A. C. Croce, M. G. Bottone et al., “Apoptosis in tumour cells photosensitized with Rose Bengal acetate is induced by multiple organelle photodamage,” Histochemistry and Cell Biology, vol. 128, no. 5, pp. 485–495, 2007.
[10]  M. G. Bottone, C. Soldani, A. Fraschini et al., “Enzyme-assisted photosensitization activates different apoptotic pathways in Rose Bengal acetate treated HeLa cells,” Histochemistry and Cell Biology, vol. 131, no. 3, pp. 391–399, 2009.
[11]  K. F. Ferri and G. Kroemer, “Organelle-specific initiation of cell death pathways,” Nature Cell Biology, vol. 3, no. 11, pp. E255–E263, 2001.
[12]  M. G. Bottone, C. Soldani, P. Veneroni, D. Avella, M. Pisu, and G. Bernocchi, “Cell proliferation, apoptosis and mitochondrial damage in rat B50 neuronal cells after cisplatin treatment,” Cell Proliferation, vol. 41, no. 3, pp. 506–520, 2008.
[13]  D. L. Bodenner, P. C. Dedon, and P. C. Keng, “Selective protection against cis-diamminedichloroplatinum(II)-induced toxicity in kidney, gut, and bone marrow by diethyldithiocarbamate,” Cancer Research, vol. 46, no. 6, pp. 2751–2755, 1986.
[14]  J. Dietrich, R. Han, Y. Yang, M. Mayer-Pr?schel, and M. Noble, “CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo,” Journal of Biology, vol. 5, article 22, 2006.
[15]  C. Soldani, M. G. Bottone, A. C. Croce, A. Fraschini, G. Bottiroli, and C. Pellicciari, “The Golgi apparatus is a primary site of intracellular damage after photosensitization with Rose Bengal acetate,” European Journal of Histochemistry, vol. 48, no. 4, pp. 443–448, 2004.
[16]  V. M. González, M. A. Fuertes, C. Alonso, and J. M. Perez, “Is cisplatin-induced cell death always produced by apoptosis?” Molecular Pharmacology, vol. 59, no. 4, pp. 657–663, 2001.
[17]  A. Mandic, J. Hansson, S. Linder, and M. C. Shoshan, “Cisplatin induces endoplasmic reticulum stress and nucleus-independent apoptotic signaling,” The Journal of Biological Chemistry, vol. 278, no. 11, pp. 9100–9106, 2003.
[18]  K. J. Cullen, Z. Yang, L. Schumaker, and Z. Guo, “Mitochondria as a critical target of the chemotheraputic agent cisplatin in head and neck cancer,” Journal of Bioenergetics and Biomembranes, vol. 39, no. 1, pp. 43–50, 2007.
[19]  W. Qian, M. Nishikawa, A. M. Haque et al., “Mitochondrial density determines the cellular sensitivity to cisplatin-induced cell death,” American Journal of Physiology, vol. 289, no. 6, pp. C1466–C1475, 2005.
[20]  M. Hirama, S. Isonishi, M. Yasuda, and H. Ishikawa, “Characterization of mitochondria in cisplatin-resistant human ovarian carcinoma cells,” Oncology Reports, vol. 16, no. 5, pp. 997–1002, 2006.
[21]  S. Nakagomi, M. J. Barsoum, E. Bossy-Wetzel, C. Sütterlin, V. Malhotra, and S. A. Lipton, “A Golgi fragmentation pathway in neurodegeneration,” Neurobiology of Disease, vol. 29, no. 2, pp. 221–231, 2008.

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