Cisplatin cis-diamminedichloroplatinum

Nephrotoxicity is a major side effect of chemotherapy. Evaluating renal toxicity from anticancer drugs uses renal slices and isolated cell suspensions of renal proximal tubules [93]. Cisplatin, cis-diamminedichloroplatinum II (CDDP), is an inorganic platinum anticancer agent that offers broad-spectrum antitumor activity against various types of animal and human tumors [94]. CDDP-induced nephrotoxicity is the most important dose-limiting factor in chemotherapy [87, 95]. Earlier studies have reported that CDDP therapy is related to cardiotoxicity [89]. 

Cancer has overtaken heart disease as the world s top killer by 2011, part of a trend that should be more than double global cancer cases and deaths by 2030. Cisplatin (cis diamminedichloroplatinum(II)) is one of the most effective anticancer drugs in the treatment of a variety of tumors and it has been clinically used widely. However, its limited usefulness in the development of resistance in tumor cells and the significant side effects have generated new areas of research, which mainly focused on searching for new metal-based... 

Cisplatin (cis-Diamminedichloroplatinum(ll)), has been used as a versatile and highly effective treatment for various cancers. Unfortunately, the amounts that can be prescribed are limited by its nephrotoxicity. Of the multiple cisplatin analogues that have been synthesized and tested,... 

The most widely used drug in this category is cisplatin. Therfeore, we have summarized below its action at the chromatin level. The anti-tumour drug cis-diamminedichloroplatinum(II) (cisplatin) is employed for the treatment of ovarian and testicular carcinomas, as well as solid tumours (Loehrer and Einhorn, 1984 Zamble and Lippard 1995). 

Kinoshita, M., Yoshimura, N., Ogata, H., Tsujino, D., Takahashi, T., Takahashi, S., Wada, Y., Someya, K., Ohno, T., Masuharra, K., Tanaka, Y. High-performance liquid-chromato-graphic analysis of unchanged cis-diamminedichloroplatinum (cisplatin) in plasma and urine with post-column derivatization. J. Chromatogr. B 529, 462-467 (1990)... 

The most extensively studied platinum-containing antitumour agent is cis-diamminedichloroplatinum(II) (cisplatin) (1) [1, 2]. As reviews covering the... 

Pinto AL and Lippard SJ (1985) Binding of the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim Biophys Acta 780 167-180. 

Reed, E. Yuspa, S. H. Zwelling, L. A. Ozols, R. F. Poirier, M. C. Quantitation of cis diamminedichloroplatinum-n cisplatin DNA-intrastrand adducts in testicular and ovarian cancer patients receiving cisplatin chemotherapy. J. Clin. Invest., 77 545-50. 1986. 

The thioredoxin system, composed of nicotinamide adenine dinucleotide phosphate (reduced form), thioredoxin and thioredoxin reductase, may be involved in the cellular sensitivity to cis-diamminedichloroplatinum (Sasada et al. 1999). HeLa cells cultured with cisplatin showed a time-and dose-dependent reduction of intracellular thioredoxin reductase activity, which was well correlated with the decrease in cell viability after exposure to cisplatin. In a cell-free system, cisplatin was found to directly inactivate the reduced form of purified human thioredoxin reductase. The cis-platin-resistant variants of HeLa cells, estabUshed by continuous exposure to cisplatin, exhibited an increased expression and activity of thioredoxin reductase as well as thioredoxin compared with the... 

In addition to hydrophobic molecules, metal complexes can be incorporated into polymeric micelles. In our recent studies [73,86,87], cis-diamminedichloroplatinum(II) (cisplatin, CDDP), a metal complex antitu-... 

Two milestones in chemistry may be addressed to the geometric isomers of diamminedichloroplatinum(II). About 100 years ago Alfred Werner laid down the principles of modem coordination chemistry with the help of isomeric [PtCl2(NH3)2] [1]. About 70 years later Barnett Rosenberg and co-workers discovered that the cis isomer is antitumor active, whereas the trans isomer is not [2,3]. Today m-[PtCl2(NH3)2] (cisplatin) is routinely used as a drug, particularly effective against testicular and ovarian cancer [4],... 

FIGURE 9.5 cis and trans Isomers of Diamminedichloroplatinum(ll), [PtCljtNHjlj]. The cis isomer, also known as cisplatin, is used in cancer treatment. 

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