ArticleNeoplasia (New York, N.Y.)
2-Methoxyestradiol exhibits a biphasic effect on VEGF-A in tumor cells and upregulation is mediated through ER-alpha: a possible signaling pathway associated with the impact of 2-ME2 on proliferative cells.
Article in Neoplasia (New York, N.Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 44 citations in OpenAlex.
- Clinical and Biological Data in Patients with Pancreatic Cancer vs. Chronic Pancreatitis-A Single Center Comparative Analysis.Diagnostics (Basel, Switzerland) · 2023Article
- Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts.Journal of cellular and molecular medicine · 2018Article
- Novel combination of 2-methoxyestradiol and cyclophosphamide enhances the antineoplastic and pro-apoptotic effects on S-180 ascitic tumour cells.Journal of cell communication and signaling · 2018Article
- A second-generation 2-Methoxyestradiol prodrug is effective against Barrett's adenocarcinoma in a mouse xenograft model.Molecular cancer therapeutics · 2013Article
- Towards non-surgical therapy for uterine fibroids: catechol-O-methyl transferase inhibitor shrinks uterine fibroid lesions in the Eker rat model.Human reproduction (Oxford, England) · 2011Article
- Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase.Fertility and sterility · 2011Article
- The in vitro effects of 2-methoxyestradiol-bis-sulphamate on cell numbers, membrane integrity and cell morphology, and the possible induction of apoptosis and autophagy in a non-tumorigenic breast epithelial cell line.Cellular & molecular biology letters · 2010Article
- MMP-2 alters VEGF expression via alphaVbeta3 integrin-mediated PI3K/AKT signaling in A549 lung cancer cells.International journal of cancer · 2010Article
- 2-methoxyestradiol inhibits Barrett's esophageal adenocarcinoma growth and differentiation through differential regulation of the beta-catenin-E-cadherin axis.Molecular cancer therapeutics · 2010Article
- Molecular genetics and racial disparities of uterine leiomyomas.Best practice & research. Clinical obstetrics & gynaecology · 2008Review
- Regulation of catechol-O-methyltransferase expression in human myometrial cells.Obstetrics and gynecology · 2006Article
- A review of the past, present, and future directions of neoplasia.Neoplasia (New York, N.Y.) · 2005Review
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5 authors at 1 institution in 1 country.
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Abstract
2-Methoxyestradiol (2-ME2) was reported to elicit both stimulation and inhibition of tumor angiogenesis and growth depending on the dosage used. However, the mechanism(s) of the biphasic action of 2-ME2 has been elusive. Here we describe a regulatory role of vascular endothelial growth factor-A (VEGF-A) in the biphasic effects on estrogen receptor (ER)+ GH3 rat pituitary tumor cells and MCF-7 human breast tumor cells depending on the dosage of 2-ME2 used. We observed that acute exposure to 2-ME2, irrespective of dosage, did not alter cellular proliferation, but enhanced the VEGF-A mRNA level. As the treatment duration increased, biphasic effect was elicited. A concentration of 1 microM 2-ME2 increased both cell proliferation and VEGF-A levels in these cells, whereas higher doses exhibited reversed impact. A low dose of 2-ME2 also increased the VEGF-A mRNA expression in ER-alpha-transfected human mammary epithelial cells (HMECs). The effect was reversed in ER- cells. The enhanced expression of VEGF-A mRNA could be blocked by the pure estrogen antagonist, ICI 182,780, and reveal that the upregulation of VEGF-A expression by 2-ME2 is mediated through ER-alpha. Furthermore, the biphasic effect of 2-ME2 on cell proliferation can be modulated by administrating VEGF-A antibodies or VEGF-A proteins. Studies also demonstrate that the VEGF-A protein, induced by 2-ME2, is functionally active and upregulates the proliferation of adjacent endothelial cells.
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