2-Methoxyestradiol in the human corpus luteum throughout the luteal phase and its influence on lutein cell steroidogenesis and angiogenic activity

Kohen, Paulina; Henríquez, Sandra; Rojas, Candy; Gerk, Phillip M.; Palomino, Wilder A.; Strauss, Jerome F.; Devoto, Luigi

doi:10.1016/j.fertnstert.2013.07.1980

Cited by 21 publications

(11 citation statements)

References 29 publications

(34 reference statements)

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“…Studies in vitro and in vivo revealed that 2-ME at pharmacological concentrations inhibited the growth of various cancer types, including colon [35], breast [36], or lung [37]. On the contrary, there are only a few data concerning physiological activity of 2-ME [17,38]. It has to be also underlined that in adult rats, the E2 content of the hippocampus is six times higher than in plasma.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line

et al. 2015

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2-methoxyestradiol, metabolite of 17β-estradiol, is considered a potential anticancer agent, currently investigated in several clinical trials. This natural compound was found to be effective towards great number of cancers, including colon, breast, lung, and osteosarcoma and has been reported to be relatively non-toxic towards non-malignant cells. The aim of the study was to determine the potential neurotoxicity and genotoxicity of 2-methoxyestradiol at physiological and pharmacological relevant concentrations in hippocampal HT22 cell line. Herein, we determined influence of 2-methoxyestradiol on proliferation, inhibition of cell cycle, induction of apoptosis, and DNA damage in the HT22 cells. The study was performed using imaging cytometry and comet assay techniques. Herein, we demonstrated that 2-methoxyestradiol, at pharmacologically and also physiologically relevant concentrations, increases nuclear localization of neuronal nitric oxide synthase. It potentially results in DNA strand breaks and increases in genomic instability in hippocampal HT22 cell line. Thus, we are postulating that naturally occurring 2-methoxyestradiol may be considered a physiological modulator of neuron survival.

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Section: Discussionmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line

et al. 2015

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“…Then, the hydroxyl group previously added is replaced by a methyl group through a conjugation reaction catalyzed by the enzyme COMT to generate a molecule of 2ME 2 [12]. As CYP1A1 and COMT are expressed in the oviduct [11]), ovary [16], endometrium [17], placenta [18,19], prostate [20] and testis [21] it is feasible to postulate that 2ME 2 could also be locally generated from E 2 in these organs.…”

Section: Generation Of 2-methoxyestradiolmentioning

confidence: 99%

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

Parada-Bustamante¹,

Valencia²,

Reuquén³

et al. 2015

MRMC

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Estradiol (E2) is a steroid hormone whose physiological actions are mainly mediated by its interaction with intracellular estrogen receptors (ER) leading to modification on the mRNA and protein synthesis in its target cells. However, estrogens can also activate several intracellular signal transduction cascades by non-genomic mechanisms. Estrogens must be inactivated and removed from blood through its conversion to soluble compounds with an apparent low estrogenic activity and decreased affinity for ER. In this context, 2-methoxyestradiol (2ME2) is generated by a sequential hydroxylation of E2 via the enzyme cytochrome P450 isoform 1A1 to produce 2-hydroxyestradiol (2OHE2) followed by a conjugation reaction catalyzed by the enzyme Catechol-O-Methyltransferase generating 2ME2 from 2OHE2. Recent evidence indicates that physiological concentration of 2ME2 may regulate several biological processes while high concentrations of this metabolite may induce pathophysiological alterations in several tissues. In the last years, 2ME2 has also been described as a promising anticancer drug although its cellular and molecular mechanisms are still being disclosed. Herein, we will review the available literature concerning the role of 2ME2 in health and disease. We will focus on to describing the intracellular mechanisms by which 2ME2 exerts its effects on reproductive and non-reproductive tissues. The promising anticancer effects of 2ME2 and its synthetic derivatives will also be discussed. Finally, a group of 2ME2-target genes that could be used as biomarkers of 2ME2 under physiological or pathophysiological conditions will be reviewed.

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“…Multiple clinical trials have used 2-ME as an efficient therapeutic agent for several types of cancer [ 7 , 13 – 17 ]. In contrast, there are only a few studies concerning the physiological activity of 2-ME [ 5 , 6 , 53 ]. In spite of its proven anticancer activity, the molecular mechanisms of 2-ME remain unclear.…”

Section: Introductionmentioning

confidence: 99%

DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol

et al. 2015

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2-Methoxyestradiol (2-ME) is a physiological metabolite of 17β-estradiol. At pharmacological concentrations, 2-ME inhibits colon, breast and lung cancer in tumor models. Here we investigated the effect of physiologically relevant concentrations of 2-ME in osteosarcoma cell model. We demonstrated that 2-ME increased nuclear localization of neuronal nitric oxide synthase, resulting in nitro-oxidative DNA damage. This in turn caused cell cycle arrest and apoptosis in osteosarcoma cells. We suggest that 2-ME is a naturally occurring hormone with potential anti-cancer properties.

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2-Methoxyestradiol in the human corpus luteum throughout the luteal phase and its influence on lutein cell steroidogenesis and angiogenic activity

Cited by 21 publications

References 29 publications

Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line

Neuronal Nitric Oxide Synthase-Mediated Genotoxicity of 2-Methoxyestradiol in Hippocampal HT22 Cell Line

Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease

DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol

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