Concentration-dependent mitogenic and antiproliferative actions of 2-methoxyestradiol in estrogen receptor-positive human breast cancer cells

Liu, Zhijian; Zhu, Bao Ting

doi:10.1016/j.jsbmb.2003.12.003

Cited by 58 publications

(59 citation statements)

References 35 publications

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“…Other laboratories have previously shown that treatment with nanomolar concentrations of 2-ME 2 induced a mitogenic response in T47D cells that they believe is mediated by ER when cultured in the absence of exogenous E 2 [Han et al 2005;Liu et al 2005;Liu and Zhu 2004;Vijayanathan et al 2006]. This study has consistently found an anti-proliferative effect of 2-ME 2 at concentrations of 1-100 nM in T47D cells, however, these results are not significant when compared to the control.…”

Section: Discussionmentioning

confidence: 59%

Effects of Estrogen Metabolite 2-Methoxyestradiol on Tumor Suppressor Protein p53 and Proliferation of Breast Cancer Cells

Siebert¹,

Sanchez²,

Dinda

et al. 2011

Systems Biology in Reproductive Medicine

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Section: Discussionmentioning

confidence: 59%

Effects of Estrogen Metabolite 2-Methoxyestradiol on Tumor Suppressor Protein p53 and Proliferation of Breast Cancer Cells

Siebert¹,

Sanchez²,

Dinda

et al. 2011

Systems Biology in Reproductive Medicine

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“…The reason for this is that 2-MeOE2 has a very low bioavailability and is rapidly inactivated by conjugation and oxidation of the hydroxyl groups at the C3/C17 positions of the oestrane nucleus (Liu et al, 2005;Newman et al, 2006). Furthermore, 2MeOE2 has been shown to exhibit mitogenic effects in ER-positive cells that were mediated through the oestrogen receptor (Liu and Zhu, 2004). Numerous analogues of 2-MeOE2 have been synthesised and tested in an attempt to improve its potency including the 2-ethoxy, 2-methoxymethyl and 14-dehydro derivatives (Cushman et al, 1995;Brueggemeier et al, 2001;Tinley et al, 2003).…”

mentioning

confidence: 99%

In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol

et al. 2007

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Drugs that inhibit growth of tumours and their blood supply could have considerable therapeutic potential. 2-Methoxyoestradiol-3,17-O,O-bis-sulphamate (2-MeOE2bisMATE) has been shown to inhibit the proliferation of MCF-7 (ER+) breast cancer cells and angiogenesis in vitro. 2-MeOE2bisMATE and its analogue, 17-Cym-2-MeOE2MATE, were investigated for their ability to inhibit in vivo angiogenesis and tumour growth. The mouse Matrigel plug assay for angiogenesis was used to investigate the effect of compounds on neovascularisation and was quantified using a FITC-dextran injection technique. Nude mice bearing tumours derived from MCF-7 cells were used to assess efficacy on tumour growth. Tumour sections were stained for VEGFR-2 and Ki67 to assess tumour angiogenesis and cell proliferation respectively. Matrigel plugs supplemented with basic fibroblast growth factor resulted in increased neovascularisation over 7 days. Oral administration of 2-MeOE2bisMATE for 7 days at 10 or 50 mg kg À1 significantly reduced neovascularisation to or below control levels respectively. 17-Cym-2-MeOE2MATE at 20 mg kg À1 was equally effective. 2-MeOE2bisMATE, dosed daily for 21 days, caused a 52% reduction in tumour growth at 5 mg kg À1 and 38% regression at 20 mg kg À1 . 17-Cym-2-MeOE2MATE (20 mg kg À1 ) reduced tumour growth by 92%. Immunohistochemistry revealed a reduction in angiogenesis and proliferation. Matrigel plug and tumour imaging after FITC-dextran injection indicated that 2-MeOE2bisMATE caused a marked disruption of vasculature. These sulphamoylated oestrogen derivatives have been shown to be potent inhibitors of angiogenesis in vivo. This, together with their ability to inhibit tumour growth, indicates the potential of this new class of drugs for further development for cancer therapy.

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“…Catecholestrogens are the major metabolites produced during estrogen metabolism (Ball & Knuppen 1980). The catecholestrogens, 2-or 4-hydroxyestrogen, can act as estrogen antagonists (Vandewalle & Lefebvre 1989, Bradlow 1996, Al-Hendy & Salama 2006, while their methylated counterparts, 2-or 4-methoxyestrogen, can act as estrogen agonists in multiple biologic assays (Banerjee et al 2003, Lippert et al 2003, Liu & Zhu 2004, Sutherland et al 2005. In this study, we monitored the longitudinal changes in urinary 2-hydroxyestrogen as an indirect indicator for the changes of estrogen metabolism in pregnant rats before, during, and after pregnancy (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In estrogen metabolism, COMT converts the catecholestrogens, 2-and 4 hydroxyestrogen, to 2-and 4-methoxyestrogen respectively (Creveling 2003). The catecholestrogens, 2-or 4-hydroxyestrogen, can act as estrogen antagonists (Vandewalle & Lefebvre 1989, Bradlow 1996, Al-Hendy & Salama 2006) while their methylated counterparts, 2-or 4-methoxyestrogen, can act as estrogen agonists in multiple biologic assays (Banerjee et al 2003, Lippert et al 2003, Liu & Zhu 2004, Sutherland et al 2005. COMT is present in many types of tissues, including those involved in reproduction, such as the placenta (Castren & Saarikoski 1974, Barnea et al 1988, the decidua vera (Casey & MacDonald 1983), the myometrium (Al-Hendy & Salama 2006, Wentz et al 2006, and the endometrium (EN; Briggs & Briggs 1973, Casey & MacDonald 1983, Al-Hendy & Salama 2006, Salih et al 2007a.…”

Section: Introductionmentioning

confidence: 99%

Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats

Wentz

Shi

et al. 2007

Reproduction

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Catechol-O-methyltransferase (COMT) enzyme catalyzes the methylation of the 2-or 4-hydroxyestrogens to 2-or 4-methoxyestrogens. Both the hydroxyestrogens and methoxyestrogens have been shown to block or enhance the effects of estrogen respectively. Our objective was to investigate the potential role of COMT in parturition and cervical ripening using a rat model. Immunohistochemistry was conducted to detect and localize the COMT protein in rat uterine tissues during pregnancy. We measured the longitudinal changes in urinary 2-hydroxyestrogen before, during, and after pregnancy in rats. Animal studies were conducted to determine the effect of treatment with a selective COMT inhibitor on (1) mifepristone-induced preterm birth and (2) cervical resistance to stretch in pregnant rats. The intensity of staining for the COMT protein differed within the luminal epithelium, uterine gland epithelium, endometrium, and myometrium during pregnancy. Levels of staining for the COMT protein in rat myometrium were highest on day 1 and lowest on days 8 and 13, but high levels returned by days 16 and 19 of pregnancy. The levels of urinary 2-hydroxyestrogen gradually increased in the first 2 weeks of pregnancy, peaked from days 16 to 18 of pregnancy, and then gradually returned to pre-pregnancy levels after delivery. The percentage of pups retained in the uterus of pregnant rats treated with both mifepristone and COMT inhibitor (48G15%) was significantly higher (P!0.05) when compared with the value of pregnant rats treated with mifepristone alone (12G4%). The resistance to stretch was significantly higher (P!0.05) in cervical tissues from the pregnant rats treated with COMT inhibitor (0.28) when compared with cervical tissues taken from rats treated with vehicle control (0.18). Modulation of COMT activity may play a role in the regulation of myometrial contractility and cervical ripening during pregnancy.

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Concentration-dependent mitogenic and antiproliferative actions of 2-methoxyestradiol in estrogen receptor-positive human breast cancer cells

Cited by 58 publications

References 35 publications

Effects of Estrogen Metabolite 2-Methoxyestradiol on Tumor Suppressor Protein p53 and Proliferation of Breast Cancer Cells

Effects of Estrogen Metabolite 2-Methoxyestradiol on Tumor Suppressor Protein p53 and Proliferation of Breast Cancer Cells

In vivo inhibition of angiogenesis by sulphamoylated derivatives of 2-methoxyoestradiol

Treatment with an inhibitor of catechol-O-methyltransferase activity reduces preterm birth and impedes cervical resistance to stretch in pregnant rats

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