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Release of Cytolytic Factors in Tumor Cells with the Use of Cisplatin and Carboplatin Ariane Leconte BIO-330-01-

A well-known chemotherapeutic drug named cisplatin, or cis -diamminedichloroplatinum (II), has been used to treat various human cancers, including cancers of the bladder, head and neck, lungs, ovaries, and testicles. Its mode of action is linked to its ability to interlink with the DNA purine bases, and subsequently to induce apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as repair enzymes being able to delete these cisplatin-DNA cross-links, enabling the cells to divide, other anti-cancer drugs, such as carboplatin, have also been used. Furthermore, to overcome drug resistance and reduce toxicity, combination therapies of cisplatin with other drugs have been highly considered. In vivo and in vitro, the anticancer drugs cisplatin and carboplatin have been shown to activate murine peritoneal macrophages. These activated macrophages have increased tumor activity mediated by tumor cell extension and contact formation, resulting in an increase and transfer of tumor cell lysosomes with eventual tumor cell lysis. 10 μg/ml of cisplatin or 50 μg/ml of carboplatin was observed for 2 and 24 h. Also, the release of various cytolytic factors, such as hydrogen peroxide, superoxide anion, interleukin-1 alpha, lysozyme, and β-N-hexosaminidase, which are also responsible for the destruction of tumor cells, appeared to show significant increases. The results of this study support the hypothesis that cisplatin and carboplatin primed macrophages can mediate lysis of the tumor cells by the secretion of cytolytic and cytostatic factors.