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 μM 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 μM 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.

• Klíčová slova
• Apoptosis, Breast cancer, Retinoid X receptor, Triorganotin isoselenocyanates,
• MeSH
• apoptóza účinky léků   MeSH
• lidé MeSH
• ligandy MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory prsu * farmakoterapie   metabolismus   patologie   MeSH
• organocínové sloučeniny * farmakologie   MeSH
• organoselenové sloučeniny farmakologie   chemie   MeSH
• proliferace buněk účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• retinoidní X receptory metabolismus   MeSH
• superoxid dismutáza 1 metabolismus   genetika   MeSH
• superoxiddismutasa metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ligandy MeSH
• organocínové sloučeniny * MeSH
• organoselenové sloučeniny MeSH
• reaktivní formy kyslíku MeSH
• retinoidní X receptory MeSH
• SOD1 protein, human MeSH Prohlížeč
• superoxid dismutáza 1 MeSH
• superoxiddismutasa MeSH
• superoxide dismutase 2 MeSH Prohlížeč
• triphenyltin MeSH Prohlížeč

The knowledge of the structure, function, and abundance of specific proteins related to the EMT process is essential for developing effective diagnostic approaches to cancer with the perspective of diagnosis and therapy of malignancies. The success of all-trans retinoic acid (ATRA) differentiation therapy in acute promyelocytic leukemia has stimulated studies in the treatment of other tumors with ATRA. This review will discuss the impact of ATRA use, emphasizing epithelial-mesenchymal transition (EMT) proteins in breast cancer, of which metastasis and recurrence are major causes of death.

• Klíčová slova
• ATRA, EMT, breast cancer, protein,
• MeSH
• epitelo-mezenchymální tranzice * MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové proteiny agonisté   metabolismus   MeSH
• nádory prsu metabolismus   mortalita   patologie   MeSH
• receptory kyseliny retinové agonisté   metabolismus   MeSH
• tretinoin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové proteiny MeSH
• receptory kyseliny retinové MeSH
• tretinoin MeSH

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
• antitumorózní látky chemie   farmakologie   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
• 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
• antitumorózní látky MeSH
• isothiokyanatany MeSH
• organocínové sloučeniny MeSH
• retinoidní X receptory MeSH
• trialkylcínové sloučeniny MeSH
• tributyltin MeSH Prohlížeč
• triphenyltin MeSH Prohlížeč

The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR. Here, we showed that triorganotin derivatives—tributyltin-chloride (TBT-Cl), tributyltin-bromide (TBT-Br), tributyltin-iodide (TBT-I) and tributyltin-isothiocyanate (TBT-NCS) or triphenyltin-chloride (TPT-Cl) and triphenyltin-isothiocyanate (TPT-NCS)—could induce the death of L1210 mice leukemia cells at a submicromolar concentration independently of P-gp overexpression. The median lethal concentration obtained for triorganotin derivatives did not exceed 0.5 µM in the induction of cell death of either P-gp negative or P-gp positive L1210 cells. Apoptosis related to regulatory pathway of Bcl-2 family proteins seems to be the predominant mode of cell death in either P-gp negative or P-gp positive L1210 cells. TBT-Cl and TBT-Br were more efficient with L1210 cells overexpressing P-gp than with their counterpart P-gp negative cells. In contrast, TBT-I and TPT-NCS induced a more pronounced cell death effect on P-gp negative cells than on P-gp positive cells. Triorganotin derivatives did not affect P-gp efflux in native cells measured by calcein retention within the cells. Taken together, we assumed that triorganotin derivatives represent substances suitable for suppressing the viability of P-gp positive malignant cells.

• Klíčová slova
• L1210 cells, P-glycoprotein, apoptosis, calcein cell retention, multidrug resistance, triorganotin derivatives,
• MeSH
• cytotoxiny * chemická syntéza   chemie   farmakokinetika   farmakologie   MeSH
• leukemie farmakoterapie   genetika   metabolismus   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• P-glykoproteiny biosyntéza   genetika   MeSH
• regulace genové exprese u leukemie účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABCB1 protein, human MeSH Prohlížeč
• cytotoxiny * MeSH
• nádorové proteiny MeSH
• P-glykoproteiny MeSH