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Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor ?.


ABSTRACT: Background:Targeting negatively charged mitochondria is often achieved using triphenylphosphonium (TPP) cations. These cationic vehicles may possess biological activity, and a docking study indicates that TPP-moieties may act as modulators of signaling through the estrogen receptor ? (ER?). Moreover, in vivo and in vitro experiments revealed the estrogen-like effects of TPP-based compounds. Here, we tested the hypothesis that TPP-based compounds regulate the activity of ER?. Methods:We used ERa-positive and ER?-negative human breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231, respectively). Cell proliferation was measured using a resazurin cell growth assay and a real-time cell analyzer assay. Cell cycle progression was analyzed using flow cytometry. Real-time PCR was used to assess mRNA expression of endogenous estrogen-responsive genes. Luciferase activity was measured to evaluate transcription driven by estrogen-responsive promoters in cells transfected with an estrogen response element (ERE)3-luciferase expression vector. Results:The TPP-based molecules SkQ1 and C12TPP, as well as the rhodamine-based SkQR1, did not increase the proliferation or alter the cell cycle progression of MCF-7 cells. In contrast, 17? estradiol increased the proliferation of MCF-7 cells and the proportion of cells in the S/G2/M-phases of the cell cycle. TPP-based compounds did not affect the induction of transcription of an ERE-luciferase expression vector in vitro, and SkQ1 did not alter the levels of expression of estrogen-dependent genes encoding GREB1, TFF1, COX6, and IGFBP4. Conclusion:TPP-based compounds do not possess properties typical of ER? agonists.

SUBMITTER: Zinovkina LA 

PROVIDER: S-EPMC7102506 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α.

Zinovkina Ludmila A LA   Galivondzhyan Alina K AK   Prikhodko Anastasia S AS   Galkin Ivan I II   Zinovkin Roman A RA  

PeerJ 20200325


<h4>Background</h4>Targeting negatively charged mitochondria is often achieved using triphenylphosphonium (TPP) cations. These cationic vehicles may possess biological activity, and a docking study indicates that TPP-moieties may act as modulators of signaling through the estrogen receptor α (ERα). Moreover, in vivo and in vitro experiments revealed the estrogen-like effects of TPP-based compounds. Here, we tested the hypothesis that TPP-based compounds regulate the activity of ERα.<h4>Methods</  ...[more]

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