Analysis of proteomic changes 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

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62157124%3A16370%2F18%3A43877158" target="_blank" >RIV/62157124:16370/18:43877158 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

Analysis of proteomic changes 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

Background Nuclear retinoid receptors (RARs) and retinoid X receptors (RXRs), which act upon binding of retinoids and rexinoids, respectively, as ligand inducible transcription factors are known to inhibit carcinogenesis, suppress premalignant epithelial lesions, tumour growth and invasion in a variety of tissues. The aim of this study was to investigate the effect of all-trans retinoic acid (RAR ligand), without or with tributyltin isothiocyanate, a potent RXR ligand on tumour cell protein profile. Method The MDA-MB-231, the oestrogen receptor negative human breast cancer cell line was selected for the gel associated proteomic strategies based on bottom-up method. 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. Results We have identified at least thirty 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. Conclusion Our data on combined effect of all-trans retinoic acid and tributyltin isothiocyanate based on proteomic analysis provide new insights into a role of RXR/RAR heterodimer. The knowledge achieved from current study offers further opportunity to study triorganotins more intensively in order to enhance antitumor effect of natural or synthetic RARs ligands and also take advantage of the fact on direct activation of RXR by triorganotins.

Název v anglickém jazyce

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

Popis výsledku anglicky

Background Nuclear retinoid receptors (RARs) and retinoid X receptors (RXRs), which act upon binding of retinoids and rexinoids, respectively, as ligand inducible transcription factors are known to inhibit carcinogenesis, suppress premalignant epithelial lesions, tumour growth and invasion in a variety of tissues. The aim of this study was to investigate the effect of all-trans retinoic acid (RAR ligand), without or with tributyltin isothiocyanate, a potent RXR ligand on tumour cell protein profile. Method The MDA-MB-231, the oestrogen receptor negative human breast cancer cell line was selected for the gel associated proteomic strategies based on bottom-up method. 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. Results We have identified at least thirty 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. Conclusion Our data on combined effect of all-trans retinoic acid and tributyltin isothiocyanate based on proteomic analysis provide new insights into a role of RXR/RAR heterodimer. The knowledge achieved from current study offers further opportunity to study triorganotins more intensively in order to enhance antitumor effect of natural or synthetic RARs ligands and also take advantage of the fact on direct activation of RXR by triorganotins.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2018

Kód důvěrnosti údajů

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