title: 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.
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91, Bratislava, Slovak Republic. exonhun@savba.sk.
authors.forename: Luba
authors.initials: L
authors.lastname: Hunakova
authors.affiliation: Laboratory of Molecular Endocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06, Bratislava, Slovak Republic.
authors.forename: D
authors.initials: D
authors.lastname: Macejova
authors.affiliation: Laboratory of Molecular Endocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06, Bratislava, Slovak Republic.
authors.forename: L
authors.initials: L
authors.lastname: Toporova
authors.affiliation: Laboratory of Molecular Endocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06, Bratislava, Slovak Republic.
authors.forename: J
authors.initials: J
authors.lastname: Brtko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D009947:Organotin Compounds / Q000494:pharmacology*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009947:Organotin Compounds; D018168:Receptors, Retinoic Acid; D014220:Trialkyltin Compounds; C011559:tributyltin; D053148:Caspase 3; D053179:Caspase 7; C012594:triphenyltin chloride
keywords: All-trans retinoic acid receptor; Cytotoxicity; Human breast carcinoma cells; Migration; Retinoid X receptor; Triorgatonins