Medicinal Chemistry

Author(s): Radim Havelek, Pavel Siman, Jana Cmielova, Alena Stoklasova, Jirina Vavrova, Jaromir Vinklarek, Jiri Knizek and Martina Rezacova

DOI: 10.2174/157340612801216364

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Differences in Vanadocene Dichloride and Cisplatin Effect on MOLT-4 Leukemia and Human Peripheral Blood Mononuclear Cells

Page: [615 - 621] Pages: 7

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Abstract

Modern chemotherapy is interested in developing new agents with high efficiency of treatment in low-dose medication strategies, lower side toxicity and stronger specificity to the tumor cells. Vanadocene dichloride (VDC) belongs to the group of the most promising metallocene antitumor agents; however, its mechanism of action and cytotoxicity profile are not fully understood. In this paper we assess cytotoxic effects of VDC in comparison to cisplatin using opposite prototype of cells; human peripheral blood mononuclear (PBMCs) cells and human acute lymphoblastic leukemia cell line (MOLT-4). Our findings showed cytotoxic effect of VDC on leukemia cells, but unfortunately on human peripheral blood mononuclear cells as well. VDC induces apoptosis in leukemia cells; the induction is, however, lower than that of cisplatin, and in contrary to cisplatin, VDC does not induce p53 up-regulation. Cytotoxic effect of VDC on leukemia cells is less pronounced than that of cisplatin and more pronounced in PBMCs than in MOLT-4 cells.

Keywords: Cisplatin, Cytotoxicity, Leukemia, MOLT-4 Cell Line, Peripheral Blood Mononuclear Cells, Vanadocene Dichloride, metallocene antitumor agents, lymphoblastic leukemia, mononuclear cells, PBMCs