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

被引:17
|
作者
Hunakova, Luba [1 ]
Horvathova, Eva [1 ]
Majerova, Karolina [1 ]
Bobal, Pavel [2 ]
Otevrel, Jan [2 ]
Brtko, Julius [3 ]
机构
[1] Slovak Acad Sci, BMC, Canc Res Inst, Dubravska Cesta 9, Bratislava 84505, Slovakia
[2] Univ Vet & Pharmaceut Sci Brno, Fac Pharm, Dept Chem Drugs, Palackeho 1946-1, Brno 61242, Czech Republic
[3] Slovak Acad Sci, Inst Expt Endocrinol, BMC, Dubravska Cesta 9, Bratislava 84505, Slovakia
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 05期
关键词
triorganotin isothiocyanates; breast cancer; cytotoxicity; apoptosis; DNA crosslinks; RETINOID-X-RECEPTORS; TRIORGANOTIN COMPOUNDS; ENDOCRINE DISRUPTION; ORGANOTIN COMPOUNDS; COMET ASSAY; DNA-DAMAGE; IN-VITRO; MODULATION; LINES; TRANSCRIPTION;
D O I
10.3390/ijms20051198
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:13
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