Mitochondria-targeted triphenylphosphonium-based compounds do not affect estrogen receptor α.
Estrogen
Targeting mitochondria
Triphenylphosphonium
Journal
PeerJ
ISSN: 2167-8359
Titre abrégé: PeerJ
Pays: United States
ID NLM: 101603425
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
11
2019
accepted:
25
02
2020
entrez:
8
4
2020
pubmed:
8
4
2020
medline:
8
4
2020
Statut:
epublish
Résumé
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. 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) The TPP-based molecules SkQ1 and C TPP-based compounds do not possess properties typical of ERα agonists.
Sections du résumé
BACKGROUND
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
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)
RESULTS
RESULTS
The TPP-based molecules SkQ1 and C
CONCLUSION
CONCLUSIONS
TPP-based compounds do not possess properties typical of ERα agonists.
Identifiants
pubmed: 32257641
doi: 10.7717/peerj.8803
pii: 8803
pmc: PMC7102506
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e8803Informations de copyright
©2020 Zinovkina et al.
Déclaration de conflit d'intérêts
The authors declare there are no competing interests.
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