Proteomic profile in human breast carcinoma MDA-MB-231 cells induced by tributyltin isothiocyanate, the biologically active ligand of nuclear retinoid X receptors.

Kód výsledku v IS VaVaI

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Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Proteomic profile in human breast carcinoma MDA-MB-231 cells induced by tributyltin isothiocyanate, the biologically active ligand of nuclear retinoid X receptors.

Popis výsledku v původním jazyce

Retinoids acting through nuclear retinoid receptors (RARs) are known to inhibit carcinogenesis, suppress premalignant epithelial lesions. tumour growth and invasion in a variety of tissues. Trialkyltin compounds, a class of organometallic compounds are known to act as nuclear retinoid X receptors (RXR) agonists. RXRs act predominantly as heterodimers with other nuclear receptors as permissive heterodimers with peroxisome proliferator-activated receptors, liver X receptors, farnesoid X receptor, pregnane X receptor and constitutive androstan receptor or as non-permissive heterodimer with vitamin D receptor, and as conditional heterodimers with retinoid receptors (RAR), and thyroid hormone receptors. Due to their capability to bind to the ligand-binding domain of RXR subtypes, they function as potent transcriptional activators (1). Some of them have been gaining growing importance in oncology, since they might affect a variety of nuclear receptor signalling pathways through their effect on RXR subtypes (2,3). The aim of this study was to investigate the effect of biologically active ligand of nuclear retinoid/retinoid X receptors of natural origin all-trans retinoic acid (RAR ligand) and freshly synthesized (commercially non-accessible) tributyltin isothiocyanate, synthetic RXR ligand and their combination on cell protein profile. The MDA-MB-231, estrogen receptor negative human breast cancer cell line was chosen as an experimental model for the gel associated proteomic strategies based on bottom-up method (4). The total cell proteins were extracted utilizing a Radio-Immunoprecipitation Assay buffer and separated on 2D sodium dodecyl sulphate polyacrylamide gel electrophoresis. After protein separation, individual 2D gel maps were analyzed, identified by MALDI-TOF/TOF and processed using PDQuestTM software. We have identified at least 30 proteins affected by tributyltin isothiocyanate. Subsequently, specific proteins associated with tumour progression were selected. We have found that tributyltin isothiocyanate in combination with all-trans retinoic acid significantly reduced protein levels of vimentin, nucleoside diphosphate kinase and glyceraldehyde-3-phospate dehydrogenase, proteins linked to metabolic processes, epithelial-mesenchymal transition or apoptosis.

Název v anglickém jazyce

Proteomic profile in human breast carcinoma MDA-MB-231 cells induced by tributyltin isothiocyanate, the biologically active ligand of nuclear retinoid X receptors.

Popis výsledku anglicky

Retinoids acting through nuclear retinoid receptors (RARs) are known to inhibit carcinogenesis, suppress premalignant epithelial lesions. tumour growth and invasion in a variety of tissues. Trialkyltin compounds, a class of organometallic compounds are known to act as nuclear retinoid X receptors (RXR) agonists. RXRs act predominantly as heterodimers with other nuclear receptors as permissive heterodimers with peroxisome proliferator-activated receptors, liver X receptors, farnesoid X receptor, pregnane X receptor and constitutive androstan receptor or as non-permissive heterodimer with vitamin D receptor, and as conditional heterodimers with retinoid receptors (RAR), and thyroid hormone receptors. Due to their capability to bind to the ligand-binding domain of RXR subtypes, they function as potent transcriptional activators (1). Some of them have been gaining growing importance in oncology, since they might affect a variety of nuclear receptor signalling pathways through their effect on RXR subtypes (2,3). The aim of this study was to investigate the effect of biologically active ligand of nuclear retinoid/retinoid X receptors of natural origin all-trans retinoic acid (RAR ligand) and freshly synthesized (commercially non-accessible) tributyltin isothiocyanate, synthetic RXR ligand and their combination on cell protein profile. The MDA-MB-231, estrogen receptor negative human breast cancer cell line was chosen as an experimental model for the gel associated proteomic strategies based on bottom-up method (4). The total cell proteins were extracted utilizing a Radio-Immunoprecipitation Assay buffer and separated on 2D sodium dodecyl sulphate polyacrylamide gel electrophoresis. After protein separation, individual 2D gel maps were analyzed, identified by MALDI-TOF/TOF and processed using PDQuestTM software. We have identified at least 30 proteins affected by tributyltin isothiocyanate. Subsequently, specific proteins associated with tumour progression were selected. We have found that tributyltin isothiocyanate in combination with all-trans retinoic acid significantly reduced protein levels of vimentin, nucleoside diphosphate kinase and glyceraldehyde-3-phospate dehydrogenase, proteins linked to metabolic processes, epithelial-mesenchymal transition or apoptosis.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30107 - Medicinal chemistry

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů