Publication details

Triphenyltin isoselenocyanate: a novel nuclear retinoid X receptor ligand with antiproliferative and cytotoxic properties in cell lines derived from human breast cancer



Year of publication 2024
Type Article in Periodical
Magazine / Source Molecular and Cellular Biochemistry
MU Faculty or unit

Faculty of Pharmacy

Keywords Triorganotin isoselenocyanates; Retinoid X receptor; Apoptosis; Breast cancer
Description Several commercially available triorganotin compounds were previously found to function as agonist ligands for nuclear retinoid X receptor (RXR) molecules. Triphenyltin isoselenocyanate (TPT-NCSe), a novel selenium atom containing a derivative of triorganotin origin, was found to represent a new cognate bioactive ligand for RXRs. TPT-NCSe displayed a concentration- and time-dependent decrease in the cell viability in both human breast carcinoma MCF-7 (estrogen receptor positive) and MDA-MB-231 (triple negative) cell lines. Reactive oxygen species levels generated in response to TPT-NCSe were significantly higher in both carcinoma cell lines treated with TPT-NCSe when compared to mock-treated samples. Treatment with 500 nM TPT-NCSe caused a decrease in SOD1 and increased SOD2 mRNA in MCF-7 cells. The levels of SOD2 mRNA were more increased following the treatment with TPT-NCSe along with 1 mu M all-trans retinoic acid (AtRA) in MCF-7 cells. An increased superoxide dismutase SOD1 and SOD2 mRNA levels were also detected in combination treatment of 500 nM TPT-NCSe and 1 mu M AtRA in TPT-NCSe-treated MDA-MB-231 cells. The data have also shown that TPT-NCSe induces apoptosis via a caspase cascade triggered by the mitochondrial apoptotic pathway. TPT-NCSe modulates the expression levels of apoptosis-related proteins, Annexin A5, Bcl-2 and BAX family proteins, and finally, it enhances the expression levels of its cognate nuclear receptor subtypes RXRalpha and RXRbeta.

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