Chemotherapy and radiotherapy are often used to treat Acute Lymphoblastic Leukemia (ALL). However, the resistance problem of treatment using the current drug in ALL patients has decreased the effectiveness of such therapy. Therefore, a study needs to be conducted to identify the potential of new anticancer agents. Organotin (IV) dithiocarbamate, an organometallic compound, causes toxic effects on cancer cells in vitro and in vivo. This study examines the cytotoxic effects and mode of cell death of novel organotin (IV) dithiocarbamate compounds of triphenyltin (IV) diisopropyldithiocarbamate (compound 1), triphenyltin (IV) diallyldithiocarbamate (compound 2) and triphenyltin (IV) diethyldithiocarbamate (compound 3) on the acute lymphoblastic leukemia cell line, CCRF CEM (CCL-119). An MTT assay was used for the determination of the cytotoxicity of the compounds by treating cells with compounds 1-3 at the highest concentration of 10 µm for 24 h. The induction of the mode of cell death for compounds 1, 2, and 3 were identified using Annexin V-FITC/PI assay. From the results, all triphenyltin (IV) dithiocarbamate compounds have substantial cytotoxic effects with IC50 values between 0.18-0.20 μm. The chemicals induced apoptosis cell death in CCL-119 cells, based on the determination of cell death mode. However, statistical analysis showed that only apoptotic cell death for treatment with compounds 1-2 is significant compared to negative controls. In conclusion, all these compounds have a high cytotoxicity effect and are able to cause cell death via apoptosis in CCL-119 cells.
The discovery of cisplatin has influenced scientists to study the anticancer properties of other metal complexes. Organotin(IV) dithiocarbamate compounds are gaining attention as anticancer agents due to their potent cytotoxic properties on cancer cells. In this study, a series of organotin compounds were assessed for their toxic effects on the Jurkat E6.1 cell line. WST-1 assay was used to determine the cytotoxic effect of the compounds and showed that six out of seven organotin(IV) dithiocarbamate compounds exhibited potent cytotoxic effects toward T-lymphoblastic leukemia cells, Jurkat E6.1 with the concentration of IC50 ranging from 0.67–0.94 µM. The apoptosis assay by Annexin V-FITC/PI staining showed that all tested compounds induced cell death mainly via apoptosis. Cell cycle analysis assessed using RNase/PI staining showed that organotin(IV) dithiocarbamate compounds induced cell cycle arrest at different phases. In conclusion, the tested organotin(IV) dithiocarbamate compounds demonstrated potent cytotoxicity against Jurkat E6.1 cells via apoptosis and cell cycle arrest at low IC50 value. However, further studies on the mechanisms of action are required to probe the possible potential of these compounds on leukemia cells before they can be developed into anti-leukemic agents.
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