Nejvíce citovaný článek - PubMed ID 29723984
Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression
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.
- Klíčová slova
- DNA crosslinks, apoptosis, breast cancer, cytotoxicity, triorganotin isothiocyanates,
- MeSH
- apoptóza účinky léků MeSH
- isothiokyanatany chemie farmakologie MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- nádory prsu farmakoterapie genetika metabolismus MeSH
- organocínové sloučeniny chemie farmakologie MeSH
- poškození DNA účinky léků MeSH
- protinádorové látky chemie farmakologie MeSH
- retinoidní X receptory metabolismus MeSH
- trialkylcínové sloučeniny chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- isothiokyanatany MeSH
- organocínové sloučeniny MeSH
- protinádorové látky MeSH
- retinoidní X receptory MeSH
- trialkylcínové sloučeniny MeSH
- tributyltin MeSH Prohlížeč
- triphenyltin MeSH Prohlížeč
