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

  title={Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease.},
  author={Alexis Parada-Bustamante and Cecilia Valencia and Patricia Reuqu{\'e}n and Patricia D{\'i}az and Ramiro Rincion-Rodriguez and Pedro A. Orihuela},
  journal={Mini reviews in medicinal chemistry},
  volume={15 5},
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… 

F-Spondin Is the Signal by Which 2-Methoxyestradiol Induces Apoptosis in the Endometrial Cancer Cell Line Ishikawa

Results show that F-spondin signaling is one of the components in the apoptotic effects of 2ME on Ishikawa cells and provide experimental evidence underlying the mechanism of action of this estrogen metabolite on cancer cells.

Effect of Interaction between 17β-Estradiol, 2-Methoxyestradiol and 16α-Hydroxyestrone with Chromium (VI) on Ovary Cancer Line SKOV-3: Preliminary Study

The beneficial action of estrogens on the toxic effect of Cr(VI), in the context of the risk of ovarian cancer, seems to be important and further studies are needed.

Effects of 2-Methoxyestradiol, a Main Metabolite of Estradiol on Hepatic ABCA1 Expression in HepG2 Cells

2-ME2 might upregulate ABCA1 expression via the PI3K/Akt/FoxO1 pathway, which thus reduces the lipid content in hepatocytes, which is significantly decreased in HepG2 cells.

The Influence of Interaction between Cadmium with 17β-Estradiol, 2-Methoxyestradiol and 16α-Hydroxyestrone on Viability and p-Glycoprotein in Ovarian Cancer Cell Line

The aim of this study was to assess the role of 17β-estradiol and its metabolites: 2-MeOE2, 16α-OHE1 in exposure to the metalloestrogen cadmium and to establish a starting point for further research in the field of interactions between estrogens and xenoestrogens in ovarian cancer.

Treatment with 2-methoxyestradiol increases endothelial nitric oxide synthase activity via scavenger receptor class BI in human umbilical vein endothelial cells.

2ME2 treatment increases HDL-dependent eNOS phosphorylation by upregulating endothelial hSR-BI/CLA-1 expression, suggesting that 2ME2 has a potential therapeutic value in the treatment of preeclampsia.

Estradiol increases IP3 by a nongenomic mechanism in the smooth muscle cells from the rat oviduct.

It is concluded that E2 increases IP3 by a nongenomic action operated by ESR1 and that involves the activation of PLC in the smooth muscle cells of the rat oviduct, suggesting that IP3 and CaMKII are involved in the contractile activity necessary to accelerate ovidUCTal egg transport.

Evaluation of 2-methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma.

In contrast to published results on endometrial cancer, endogenous serum 2-ME levels in MM were not found to be correlated with tumour stage and did not appear to be a suitable prognostic factor in MM.

2‐hydroxyoestradiol and 2‐methoxyoestradiol, two endogenous oestradiol metabolites, induce DNA fragmentation in Sertoli cells

The hypothesis that elevated intratesticular 2 OHE2 or 2ME2 concentrations could be related to male infertility since 2OHE2 by apoptosis and2ME2 by undetermined mechanisms induce DNA fragmentation in Sertoli cells is supported.



Cytochrome P450-mediated metabolism of estrogens and its regulation in human.

Functional role of estrogen metabolism in target cells: review and perspectives.

Some of the many actions of estradiol may not be caused by est radiol per se, but may result from the formation of active estrogen metabolite(s) which function as local mediators or may activate their own unique receptors or effectors.

Immunomodulation by the estrogen metabolite 2-methoxyestradiol.

Mechanism of action of 2-methoxyestradiol: new developments.

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2-methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathway.

2ME2 treatment results in up-regulation of death receptor 5 (DR5) protein expression in vitro and in vivo and renders cells more sensitive to the cytotoxic activities of the DR5 ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

2-Methoxyestradiol and Disorders of Female Reproductive Tissues

The involvement of 2ME in reproductive pathophysiology is discussed and its known mechanisms of action are summarized: microtubule disruption, inhibition of angiogenesis and stimulation of apoptosis.

Intracellular signaling pathways: nongenomic actions of estrogens and ligand-independent activation of estrogen receptors.

It is clear that estrogens, ERs and intracellular signaling pathways are intimately linked and this review will explore the relationship between these components of the estrogen-ER signal transduction process.

Estradiol Metabolites Inhibit Endothelin Synthesis by an Estrogen Receptor-Independent Mechanism

The findings indicate that the estradiol metabolites 2-hydroxyestradiol and 2-methoxyestradio potently inhibit endothelin-1 synthesis by means of an estrogen receptor-independent mechanism and may contribute to the cardioprotective effects of estradio.