Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α
| Autor: | Ludmila A Zinovkina, Ivan I. Galkin, Roman A. Zinovkin, Alina Kh. Galivondzhyan, Anastasia S. Prikhodko |
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| Rok vydání: | 2020 |
| Předmět: |
lcsh:Medicine
Estrogen receptor Targeting mitochondria Biochemistry General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Molecular Biology 030304 developmental biology Hormone response element 0303 health sciences Expression vector Chemistry Cell growth General Neuroscience lcsh:R 030302 biochemistry & molecular biology Biological activity Cell Biology General Medicine Transfection Cell cycle Triphenylphosphonium Estrogen Cell biology GREB1 General Agricultural and Biological Sciences |
| Zdroj: | PeerJ PeerJ, Vol 8, p e8803 (2020) |
| ISSN: | 2167-8359 |
| DOI: | 10.7717/peerj.8803 |
| Popis: | 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 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. Methods We used ERa-positive and ERα-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, 17β 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 ERα agonists. |
| Databáze: | OpenAIRE |
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