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.

Result code in 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>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

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.

Original language description

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.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30107 - Medicinal chemistry

Project

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Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2018

Confidentiality

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