In vitro evaluation of the cytotoxic and bactericidal mechanism of the commonly used pesticide triphenyltin hydroxide

Abstract

Triphenyltin hydroxide (TPTH) is a widely used pesticide that is highly toxic to a variety of organisms including humans and a potential contender for the environmental pollutant. In the present study, the cytotoxic mechanism of TPTH on mammalian cells was analyzed using HeLa cells and the antibacterial activity was analyzed using B. subtilis and E. coli cells. TPTH inhibited the growth of HeLa cells with a half-maximal inhibitory concentration of 0.25 μM and induced mitotic arrest. Immunofluorescence microscopy analysis showed that TPTH caused strong depolymerization of interphase microtubules and spindle abnormality with the appearance of colchicine type mitosis and condensed chromosome. TPTH exhibited high affinity for tubulin with a dissociation constant of 2.3 μM and inhibited the in vitro microtubule assembly in the presence of glutamate as well as microtubule-associated proteins. Results from the molecular docking and in vitro experiments implied that TPTH may have an overlapping binding site with colchicine on tubulin with a distance of about 11 Å between them. TPTH also binds to DNA at the A-T rich region of the minor groove. The data presented in the study revealed that the toxicity of TPTH in mammalian cells is mediated through its interactions with DNA and its strong depolymerizing activity on tubulin. However, its antibacterial activity was not through FtsZ, the prokaryotic homolog of tubulin but perhaps through its interactions with DNA.