Triphenyltin(IV) dithiocarbamate compound induces genotoxicity and cytotoxicity in K562 human erythroleukemia cells primarily via mitochondria-mediated apoptosis.

The novel di-and triphenyltin(IV) dithiocarbamate compounds represented as RnSnL2 (where R = C4H9, C6H5; n = 2,3; L = N,N-dithiocarbamate), Ph2Sn(N,N-diisopropyldithiocarbamate) (OC1), Ph3Sn(N,N-diisopropyldithiocarbamate) (OC2), Ph2Sn(N,N-diallyldithiocarbamate) (OC3), Ph3Sn(N,N-diallyldithiocarbamate) (OC4), and Ph2Sn(N,N-diethyldithiocarbamate) (OC5) were assessed for their cytotoxicity in K562 human erythroleukemia cells. All compounds inhibited the growth of cells at low micromolar concentrations (<10 µM), and the mechanism underlying their antiproliferative effects on K562 cells was apoptosis, as corroborated by the exposure of plasma membrane phosphatidylserine. OC2, which showed the most promising antiproliferative activity, was selected for further analyses. The results demonstrated that OC2 induced apoptosis in K562 cells via an intrinsic mitochondrial pathway triggered upon DNA damage, an early apoptotic signal. Subsequently, OC2 produced excessive intracellular reactive oxygen species. The role of oxidative stress was corroborated by the significant reduction in GSH levels and percentage of apoptosis in NAC-pretreated cells. OC2 could arrest the cell cycle progression in the S phase. These new findings elucidate the antiproliferative potential of OC2 in the K562 human erythroleukemia cells and warrant further investigation, specifically to determine the exact signaling pathway underlying its antileukemic efficacy.

Cellular Basis of Organotin(IV) Derivatives as Anticancer Metallodrugs: A Review.

Organotin(IV) compounds have wide applications in industrial and agricultural fields owing to their ability to act as poly(vinyl chloride) stabilizers and catalytic agents as well as their medicinal properties. Moreover, organotin(IV) compounds may have applications as antitumor, anti-inflammatory, antifungal, or antimicrobial agents based on the observation of synergistic effects following the binding of their respective ligands, resulting in the enhancement of their biological activities. In this review, we describe the antiproliferative activities of organotin(IV) compounds in various human cancer cell lines based on different types of ligands. We also discuss the molecular mechanisms through which organotin(IV) compounds induce cell death via apoptosis through the mitochondrial intrinsic pathway. Finally, we present the mechanisms of cell cycle arrest induced by organotin(IV) compounds. Our report provides a basis for studies of the antitumor activities of organotin(IV) compounds and highlights the potential applications of these compounds as anticancer metallodrugs with low toxicity and few side effects.