Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor alphaстатьяИсследовательская статьяЭлектронная публикация
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Дата последнего поиска статьи во внешних источниках: 7 июля 2020 г.
Аннотация:Targeting to the negatively charged mitochondria is often achieved by positively charged triphenylphosphonium (TPP) cations. This cation-vehicle can possess its own biological activity: a previous docking study suggests that TPP-moieties may act as the estrogen receptor α (ERα) modulators. Moreover, some in vivo and in vitro experiments revealed estrogen-like action of TPP-based compounds. This study aimed at testing the hypothesis that TPP-based compounds may act as the estrogen receptor α (ERα) modulators. To test this hypothesis we have carried out in vitro experiments on human breast adenocarcinoma ERα-positive MCF-7 and ERα-negative MDA-MB-231 cells. Cell proliferation was measured by resazurin cell growth assay and in the real-time cell analyzer assay. Cell cycle progression was analyzed by flow cytometry. Transcription from estrogen-responsive promoters was measured by using estrogen response element (ERE)3-luciferase transfection and also by real-time PCR. The TPP-based SkQ1 and C12TPP, as well as the rhodamine-based SkQR1, did not increase proliferation of MCF-7 cells and did not affect the cell cycle progression in MCF-7 cells. At the same time, 17𝛽 estradiol increased both MCF-7 cell proliferation and the proportion of cells in S/G2/M-phases. No TPP-based compounds affected the induction of an ERE-luciferase expression in vitro. Additionally, SkQ1 did not change the mRNA expression of estrogen-dependent genes GREB1, TFF1, COX6, and IGFBP4. Conclusion: The TPP-based compounds do not possess properties typical for ERα agonists.