Triorganotin derivates: time-dependent expression of Vimentin, Annexin A5 and selected nuclear receptors mRNA in MDA-MB-231 breast cancer cells

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

Triorganotin derivates: time-dependent expression of Vimentin, Annexin A5 and selected nuclear receptors mRNA in MDA-MB-231 breast cancer cells

Popis výsledku v původním jazyce

Trirganotin compounds are typical environmental contaminants that are used as biocides, agricultural fungicides, wood preservatives, and special paints for marine ships and endocrine disrupters. A remarkable breakthrough in this field has been found that the triorganotin compounds are agonists of the RXR nuclear receptor subtypes. Vimentin plays a very important role in the process of metastasis and its expression is typical for neoplastic cells with metastatic properties. The observed protein is a key element regulating the expression of the EMT-related transcription factors and thus it is associated with the metastatic spread of cancer. In addition, overexpression of Vimentin indicates the aggressive and invasive type of breast cancer. Annexin 5 is the protein playing an anti-apoptotic role, promoting metastatic process and progression of breast cancer. In this study, in vitro the effects of triorganotin ligands of nuclear retinoid X receptors in human MDA-MB-231 breast cancer cells were analysed. The cells were exposed to tributyltin and triphenyltin derivatives (TBT-Cl, TPT-Cl, TBT-ITC, TPT-ITC), 9-cis retinoic acid (9cRA) (100 nM) and/or all-trans retinoic acid (ATRA) (1 ?M) for 6, 12, 24 and 48 hours. Expression of mRNA genes for Vimentin, Annexin A5 and selected nuclear receptors was analyzed by semi-quantitative real-time PCR. ATRA, 9cRA and tributyltin derivatives alone or in combination with ATRA, was found to significantly induce the expression of Vimentin and Annexin A5 mRNA after 6 h. However, after 12 h and 24 h the expression was decreased and these effects were fully manifested after 48 hours of cultivation with the substances. In the case of RARbeta receptors, the action of triorganotin derivatives resulted in increased gene expression after all time ranges, with the combined effect with ATRA resulting in a synergistic enhancement of expression. Expression of RARgamma mRNA was found significantly increased after 6 hours, but after 24 and 48 hours the increase was diminished. After 6 hours after administration of retinoic acids and triorganotin derivatives, expression of RXRalpha was increased, but a decrease in expression was observed after 48 hours in cells treated with TBT-Cl and ATRA alone and with combination of ATRA with triorganotin derivatives. Given the role of vimentin in the epithelial-mesenchymal transition process and annexin A5 in the membrane repair process, the synergistic effect of triorganotin compounds, and the ATRA mediated by RXR/RAR heterodimer could represent a promising opportunity to inhibit metastasis of aggressive forms of hormone-resistant tumours

Název v anglickém jazyce

Triorganotin derivates: time-dependent expression of Vimentin, Annexin A5 and selected nuclear receptors mRNA in MDA-MB-231 breast cancer cells

Popis výsledku anglicky

Trirganotin compounds are typical environmental contaminants that are used as biocides, agricultural fungicides, wood preservatives, and special paints for marine ships and endocrine disrupters. A remarkable breakthrough in this field has been found that the triorganotin compounds are agonists of the RXR nuclear receptor subtypes. Vimentin plays a very important role in the process of metastasis and its expression is typical for neoplastic cells with metastatic properties. The observed protein is a key element regulating the expression of the EMT-related transcription factors and thus it is associated with the metastatic spread of cancer. In addition, overexpression of Vimentin indicates the aggressive and invasive type of breast cancer. Annexin 5 is the protein playing an anti-apoptotic role, promoting metastatic process and progression of breast cancer. In this study, in vitro the effects of triorganotin ligands of nuclear retinoid X receptors in human MDA-MB-231 breast cancer cells were analysed. The cells were exposed to tributyltin and triphenyltin derivatives (TBT-Cl, TPT-Cl, TBT-ITC, TPT-ITC), 9-cis retinoic acid (9cRA) (100 nM) and/or all-trans retinoic acid (ATRA) (1 ?M) for 6, 12, 24 and 48 hours. Expression of mRNA genes for Vimentin, Annexin A5 and selected nuclear receptors was analyzed by semi-quantitative real-time PCR. ATRA, 9cRA and tributyltin derivatives alone or in combination with ATRA, was found to significantly induce the expression of Vimentin and Annexin A5 mRNA after 6 h. However, after 12 h and 24 h the expression was decreased and these effects were fully manifested after 48 hours of cultivation with the substances. In the case of RARbeta receptors, the action of triorganotin derivatives resulted in increased gene expression after all time ranges, with the combined effect with ATRA resulting in a synergistic enhancement of expression. Expression of RARgamma mRNA was found significantly increased after 6 hours, but after 24 and 48 hours the increase was diminished. After 6 hours after administration of retinoic acids and triorganotin derivatives, expression of RXRalpha was increased, but a decrease in expression was observed after 48 hours in cells treated with TBT-Cl and ATRA alone and with combination of ATRA with triorganotin derivatives. Given the role of vimentin in the epithelial-mesenchymal transition process and annexin A5 in the membrane repair process, the synergistic effect of triorganotin compounds, and the ATRA mediated by RXR/RAR heterodimer could represent a promising opportunity to inhibit metastasis of aggressive forms of hormone-resistant tumours

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

2019

Kód důvěrnosti údajů

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