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.
- MeSH
- Apoptosis drug effects MeSH
- Humans MeSH
- Ligands MeSH
- MCF-7 Cells MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms * drug therapy metabolism pathology MeSH
- Organotin Compounds * pharmacology MeSH
- Organoselenium Compounds pharmacology chemistry MeSH
- Cell Proliferation drug effects MeSH
- Reactive Oxygen Species metabolism MeSH
- Retinoid X Receptors metabolism MeSH
- Superoxide Dismutase-1 metabolism genetics MeSH
- Superoxide Dismutase metabolism MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
An attempt has been made to delineate the role of natural and synthetic retinoid receptor ligands on vimentin expression in the human triple-negative breast cancer cells. The effects of currently synthesized triorganotin derivatives of the general formula R3SnX (R is butyl or phenyl, X is isothiocyanate), which are considered RXR ligands, were investigated in the human MDA-MB-231 breast cancer cell line. Studies were evaluated in the presence and absence of all-trans retinoic acid (ATRA), a natural RAR ligand. Vimentin represents the major protein associated with epithelial-mesenchymal transition (EMT), an essential process when the primary tumour transforms into a malignant one. mRNA and proteomic data obtained in this study, based on the PDQuest software protein evaluation and further quantification of proteins by iTRAQ analysis, suggest that vimentin was significantly reduced in the combination of RAR ligand and RXR ligand treatment. Both tested triorganotin compounds showed similarly reduced expression of vimentin, but tributyltin isothiocyanate (TBT-ITC) proved to be more effective than triphenyltin isothiocyanate (TPT-ITC). Furthermore, the effect of natural (9cRA) and synthetic RXR ligands, both chloride and isothiocyanate derivatives, on vimentin expression was compared.
- MeSH
- Electrophoresis, Gel, Two-Dimensional MeSH
- Antineoplastic Agents pharmacology MeSH
- Down-Regulation MeSH
- Epithelial-Mesenchymal Transition drug effects MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms drug therapy metabolism pathology MeSH
- Organotin Compounds pharmacology MeSH
- Proteomics methods MeSH
- Retinoid X Receptors agonists metabolism MeSH
- Signal Transduction drug effects MeSH
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MeSH
- Tandem Mass Spectrometry MeSH
- Tretinoin pharmacology MeSH
- Trialkyltin Compounds pharmacology MeSH
- Vimentin metabolism MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- Publication type
- Meeting Abstract MeSH
This work aimed to provide, in one isolation and separation step, an overview of the content of proteins with different solubility after treatment with all-trans retinoic acid, which is considered to be an important therapeutic agent, predominantly in acute promyelocytic leukemia. Breast, ovarian, bladder, and skin cancers have been demonstrated to be suppressed by retinoic acid, as well. The bottom-up proteomic strategies were applied for the analysis of proteins extracted from triple-negative breast cancer MDA-MB-231 cells utilizing a commercially manufactured kit. The gel electrophoresis followed by MALDI-TOF MS analysis was used for protein determination. By employing PDQuest™ software, we identified several proteins affected by all-trans retinoic acid. Two proteins, vimentin and CD44, which are associated with the epithelial-mesenchymal transition, were selected for a detailed study. We have found that all-trans retinoic acid results in significantly reduced levels of vimentin and CD44 in both the cytoplasmic and membrane fractions. A significant effect was particularly evident in CD44, where protein level in the cytoplasmic fraction was almost completely suppressed.
- Publication type
- Meeting Abstract MeSH
Trialkyltins and triaryltins function as nuclear retinoid X receptors (RXR) agonists due to their affinity to the ligand-binding domain of RXR subtypes and function as transcriptional activators. We present the data on combined effects of all-trans retinoic acid (ATRA), retinoic acid receptor (RAR) ligand and tributyltin chloride or triphenyltin chloride (RXR ligands) on protein pattern in MDA-MB-231 cells. Proteomic strategies based on bottom-up method were applied in this study. The total cell proteins were extracted, separated on 2D SDS-PAGE and their characterization was achieved by MALDI-TOF/TOF MS/MS. By employing PDQuest™ software, we identified more than 30 proteins differently affected by the above compounds. For further studies, we selected specific proteins associated either with metabolic pathway (glyceraldehyde-3-phosphate dehydrogenase) or to cellular processes as apoptosis, regulation of gene transcription or epithelial-mesenchymal transition (annexin 5, nucleoside diphosphate kinase B and vimentin). We have found that treatment of MDA-MB-231 cells with triorganotins reduced the expression of studied proteins. Moreover, the treatment of MDA-MB-231 cells with triorganotin compounds together with ATRA resulted in an additional reduction of annexin 5, vimentin and nucleoside diphosphate kinase B. These results demonstrate that RXR/RAR heterodimer may act under this experimental design as permissive heterodimer allowing activation of RXR by triorganotins.
- MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Breast Neoplasms * drug therapy pathology MeSH
- Organotin Compounds * pharmacology MeSH
- Proteomics * MeSH
- Tandem Mass Spectrometry MeSH
- Tretinoin * pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Publication type
- Meeting Abstract MeSH
- Publication type
- Meeting Abstract MeSH
In the present study, we analyzed the cell lysates of human tumour cell lines representing two major clinically different types of breast cancer. Our main goal was to show the differences between them on proteomic level. Gel electrophoresis followed by MALDI-TOF MS analysis was used for proteins determination. Exactly 98 proteins were unequivocally identified and 60 of them were expressed differentially between MDA-MB-231 and MCF-7 cell lines. Among the proteins reported here, some well-known breast cancer markers (e.g., annexin A1, annexin A2 and vimentin) were identified in the MDA-MB-231 cell line and thus we were able to distinguish both cell lines sufficiently.
- MeSH
- Humans MeSH
- MCF-7 Cells MeSH
- Biomarkers, Tumor metabolism MeSH
- Neoplasm Proteins metabolism MeSH
- Breast Neoplasms metabolism pathology MeSH
- Proteome metabolism MeSH
- Receptors, Estrogen metabolism MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Publication type
- Meeting Abstract MeSH
