Genotoxic Effects of Tributyltin and Triphenyltin Isothiocyanates, Cognate RXR Ligands: Comparison in Human Breast Carcinoma MCF 7 and MDA-MB-231 Cells

Abstract

The cytotoxicity of two recently synthesized triorganotin isothiocyanate derivatives, nuclear retinoid X receptor ligands, was tested and compared in estrogen-receptor-positive MCF 7 and -negative MDA-MB-231 human breast carcinoma cell lines. A 48 h MTT assay indicated that tributyltin isothiocyanate (TBT-ITC) is more cytotoxic than triphenyltin isothiocyanate (TPT-ITC) in MCF 7 cells, and the same trend was observed in the MDA-MB-231 cell line. A comet assay revealed the presence of both crosslinks and increasing DNA damage levels after the 17 h treatment with both derivatives. Differences in cytotoxicity of TBT-ITC and TPT-ITC detected by FDA staining correspond to the MTT data, communicating more pronounced effects in MCF 7 than in the MDA-MB-231 cell line. Both derivatives were found to cause apoptosis, as shown by the mitochondrial membrane potential (MMP) depolarization and caspase-3/7 activation. The onset of caspase activation correlated with MMP dissipation and the total cytotoxicity more than with the amount of active caspases. In conclusion, our data suggest that the DNA damage induced by TBT-ITC and TPT-ITC treatment could underlie their cytotoxicity in the cell lines studied.

Triorganotin complexes in cancer chemotherapy: Mechanistic insights and future perspectives

“…Tri ‐n‐ butyltin ( 8 ) and triphenyltin isothiocyanates ( 9 ) caused mitochondrial membrane depolarization in both MCF‐7 and MDA‐MB‐231 cells. [ 28 ] Moreover, an elevation in the levels of activated caspase‐3 and caspase‐7 was also observed for both cells, indicating the involvement of apoptosis in cell death mediated by 8 and 9 . As the breakdown in mitochondrial integrity is an initial apoptotic step in the intrinsic pathway, it can be concluded that these complexes caused apoptosis in breast cancer cells by modulating the intrinsic pathway.…”

“…Recently, complex 8 was found to be more active than complex 9 in both the MDA‐MB‐231 and MCF‐7 cell lines. [ 28 ] The authors hypothesized that the differential activity of 8 and 9 could be attributed to varied regulation of the key components in retinoid/estrogen signaling crosstalk.…”

“…The September 2014 release of the cancer screening data from the NCI reported over 350 organotin complexes with potential anticancer activity. [2] Generally, the tin (Sn) atom of organotin complexes with the formula RSnL covalently binds to one (or more) organic alkyl or aryl group, R, or ligand, L. An organotin Table 2 [ 17,18,20,26] 3 [19,21,26,27] 4 - [19,20] 5 - [19,20] 6 - [19] 8 - [20,28] 9 - [20] 10 - [29,30] 11 - [30] 12 >1,000 -- [32] 17 >1,000 -- [33] 19 - [41,42] 27 - [41,42] 29 - [44] 34 - [44] 35 >1,000 -- [46] 37 >1,000 -- [46] 40 42 [a] Figure 2…”

Triorganotin Isothiocyanates Affect Migration and Immune Check-point Receptors in Human Triple-negative Breast Carcinoma MDA-MB-231 Cells

“…NMR spectra were measured on a JEOL ECZR-400 MHz spectrometer (Jeol Ltd., Akishima, Tokyo, Japan). The purities of the prepared triorganotin compounds (tributyltin isothiocyanate and triphenyltin isothiocyanate) were better than 97%, as determined by NMR (17).…”

“…In our very recent study, we combined the anticancer/ genotoxic properties of two chemically different types of molecules, triorganotins and ITCs, into tributyltin isothiocyanate and triphenyltin isothiocyanate, and showed/compared their genotoxic effects in human breast carcinoma MCF 7 and MDA-MB-231 cells (17). Therefore, the aim of this study was to assess the biological effects of non-genotoxic concentrations of triorganotin isothiocyanates in the more aggressive, triple-negative MDA-MB-231 cells.…”