Anticancer effects of tributyltin chloride and triphenyltin chloride in human breast cancer cell lines MCF-7 and MDA-MB-231

Abstract

Triorganotin compounds induce hormonal alterations, i.e., endocrine-disrupting effects in mammals, including humans. Tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) are known to function as nuclear retinoid X receptor (RXR) agonists. Their cytotoxic effects in ER(+) luminal human breast cancer cell line MCF-7 and ER(-) basal-like human breast cancer cell line MDA-MB-231 were examined. We observed significantly higher toxicity of TBT-Cl in comparison with TPT-Cl in both cell lines. Comparable apoptosis-inducing concentrations were 200 and 800 nM, respectively, as shown by PARP cleavage and FDA staining. Both compounds activated executive caspases in the concentration-dependent manner in MDA-MB-231 cells, but the onset of TPT-Cl-induced caspase-3/7 activation was delayed in comparison with TBT-Cl. Both compounds slowed down the migration of these highly invasive cells, which was accompanied by RARbeta upregulation. Other RAR and RXR expressions were differentially modulated by studied organotins in both cell lines.

Mutant p53: a novel target for the treatment of patients with triple‐negative breast cancer?

“…It could be argued that the decreased ability of PRIMA‐1 MET to induce apoptosis in this cell line is due to the absence of caspase 3 . However, although MCF7 cells have been shown to be resistant to ionizing radiation‐induced apoptosis, possibly due to the deficiency in caspase 3, they undergo apoptosis in response to several different stimuli, including a range of different chemical compounds as well as various anti‐cancer drugs . This induction of apoptosis in caspase 3 deficient cells appears to be mediated by increased expression of compensatory caspases …”

Effect of IDH3a on glucose uptake in lung adenocarcinoma: A pilot study based on [18F]FDG

“…Tributyltin is an organotin compound that is an endocrine disruptor similar to androgen. The tumor suppressive effect of tributyltin was focused on in recent studies . Yamada et al found in a series of studies that low levels of tributyltin specifically bind to IDH3ɑ to inhibit enzyme activity, which may lead to new strategies on anti‐tumor metabolic therapy targeting IDH3ɑ.…”

“…The tumor suppressive effect of tributyltin was focused on in recent studies. 38,39 Yamada et al found in a series of studies that low levels of tributyltin specifically bind to IDH3ɑ to inhibit enzyme activity, 40,41 which may lead to new strategies on anti-tumor metabolic therapy targeting IDH3ɑ. The relatively small and available sample of this study is a limitation.…”

The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals

“…Moreover, eff ects of triorganotins have been shown on epigenetic regulation of gene expression (Stel and Legler 2015). Since recent studies have also shown that triorganotin compounds can exhibit anti-tumor activity (Tabassum and Pettinary 2006;Hunakova et al 2015;Macejova et al 2015), the further studies on triorganotin compound characteristics and action are essential.…”