2 Methoxyestrone

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Chantal Guillemette - One of the best experts on this subject based on the ideXlab platform.

  • Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression
    British Journal of Cancer, 2021
    Co-Authors: Jean-philippe Emond, Louis Lacombe, Patrick Caron, Véronique Turcotte, David Simonyan, Armen Aprikian, Fred Saad, Michel Carmel, Simone Chevalier, Chantal Guillemette
    Abstract:

    Background Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. Methods Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery ( n  = 259) and validation ( n  = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives ( n  = 15), were measured using mass spectrometry (MS). Results The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-Methoxyestrone were associated with an increased risk of development of metastasis/deaths. Conclusions Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-Methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.

  • Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression.
    British journal of cancer, 2021
    Co-Authors: Jean-philippe Emond, Louis Lacombe, Patrick Caron, Véronique Turcotte, David Simonyan, Armen Aprikian, Fred Saad, Michel Carmel, Simone Chevalier, Chantal Guillemette
    Abstract:

    Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery (n = 259) and validation (n = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives (n = 15), were measured using mass spectrometry (MS). The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-Methoxyestrone were associated with an increased risk of development of metastasis/deaths. Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-Methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.

M J Reed - One of the best experts on this subject based on the ideXlab platform.

  • the role of 17β hydroxysteroid dehydrogenases in modulating the activity of 2 methoxyestradiol in breast cancer cells
    Cancer Research, 2006
    Co-Authors: Simon P. Newman, Mathew P. Leese, Barry V L Potter, M J Reed, Christopher R Ireson, Helena J Tutill, Joanna M Day, Michael F C Parsons, Atul Purohit
    Abstract:

    The bis-sulfamoylated derivative of 2-methoxyestradiol (2-MeOE2), 2-methoxyestradiol-3,17-O,O-bis-sulfamate (2-MeOE2bisMATE), has shown potent antiproliferative and antiangiogenic activity in vitro and inhibits tumor growth in vivo. 2-MeOE2bisMATE is bioavailable, in contrast to 2-MeOE2 that has poor bioavailability. In this study, we have examined the role of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2 in the metabolism of 2-MeOE2. In MDA-MB-231 cells, which express high levels of 17beta-HSD type 2, and in MCF-7 cells transfected with 17beta-HSD type 2, high-performance liquid chromatography analysis showed that a significant proportion of 2-MeOE2 was metabolized to inactive 2-Methoxyestrone. Furthermore, MCF-7 cells transfected with 17beta-HSD type 2 were protected from the cytotoxic effects of 2-MeOE2. In contrast, no significant metabolism of 2-MeOE2bisMATE was detected in transfected cells and 17beta-HSD type 2 transfection did not offer protection against 2-MeOE2bisMATE cytotoxicity. This study may go some way to explaining the poor bioavailability of 2-MeOE2, as the gastrointestinal mucosa expresses high levels of 17beta-HSD type 2. In addition, this study shows the value of synthesizing sulfamoylated derivatives of 2-MeOE2 with C17-position modifications as these compounds have improved bioavailability and potency both in vitro and in vivo.

  • Non-steroidal and steroidal sulfamates: new drugs for cancer therapy.
    Molecular and Cellular Endocrinology, 2001
    Co-Authors: A. Purohit, Barry V L Potter, L. W. L. Woo, D Barrow, Hatem Hejaz, R.i. Nicholson, M J Reed
    Abstract:

    Abstract The development of inhibitors to block the formation of estrone and 5-androstenediol from sulfated precursors is an important new strategy for the treatment of breast cancer. In this study a series of tricyclic coumarin sulfamates (665-668 COUMATE) and a tricyclic oxepin sulfamate have been synthesised and tested for their ability to inhibit estrone sulfatase activity (E1-STS). In addition the effect of the steroid-based E1-STS inhibitor, 2-Methoxyestrone-3- O -sulfamate (2-MeOEMATE) on the morphology of MDA-MB-231 cells and breast tumour-derived fibroblasts was also examined. The tricyclic coumarin sulfamates and oxepin sulfamate were potent inhibitors of E1-STS activity with IC 50 s ranging from 8 to 250 nM. Of this series 667 COUMATE was the most potent inhibitor (IC 50  = 8 nM) and was three-times more potent than estrone-3- O -sulfamate (EMATE, IC 50  = 25 nM). 667 COUMATE did not stimulate the growth of MCF-7 breast cancer cells and is therefore devoid of estrogenicity. In vivo, 667 COUMATE inhibited E1-STS activity in rat liver tissue to a similar extent to that of EMATE. 2-MeOEMATE had a marked effect on the morphology of MDA-MB-231 cells and breast tumour-derived fibroblasts causing a significant increase in the number of rounded cells. 667 COUMATE and 2-MeOEMATE therefore offer considerable potential for development for cancer therapy.

  • Inhibition of deoxyglucose uptake in MCF-7 breast cancer cells by 2-Methoxyestrone and 2-Methoxyestrone-3-O-sulfamate.
    Molecular and cellular endocrinology, 2000
    Co-Authors: A Singh, A. Purohit, Hatem Hejaz, B V Potter, M J Reed
    Abstract:

    Most cancer cells are dependent on glucose uptake to fulfil their energy requirements. In the present investigation we have examined the ability of 2-Methoxyestrone (2-MeOE1), 2-methoxyestradiol (2-MeOE2), 2-Methoxyestrone-3-O-sulfamate (2-MeOEMATE), and a number of related compounds, to inhibit 2-deoxy-D-[1-(3)H]-glucose uptake in MCF-7 breast cancer cells. Glucose uptake was shown to be linear with respect to cell number and time over a 5-35min period. 2-MeOE2, 2-MeOE1 and 2-MeOEMATE inhibited glucose uptake by 25-49% at 10 microM. 2-Hydroxyestradiol and estrone sulfate had little effect on glucose uptake, whereas estrone glucuronide inhibited uptake by 29%. There is evidence that 2-methoxyestrogens may exert an anti-mitotic effect on cells by stabilizing microtubules in a similar manner to that of paclitaxel. We therefore examined the effect of exposing cells to 2-MeOEMATE or paclitaxel for 24 h on basal or insulin stimulated glucose uptake. Using these conditions, 2-MeOEMATE and paclitaxel inhibited basal glucose uptake by 50 and 22%, respectively, and insulin stimulated uptake by 36 and 51%, respectively. The development of drugs that can inhibit glucose uptake could have therapeutic potential for the treatment of breast cancer.

Jean-philippe Emond - One of the best experts on this subject based on the ideXlab platform.

  • Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression
    British Journal of Cancer, 2021
    Co-Authors: Jean-philippe Emond, Louis Lacombe, Patrick Caron, Véronique Turcotte, David Simonyan, Armen Aprikian, Fred Saad, Michel Carmel, Simone Chevalier, Chantal Guillemette
    Abstract:

    Background Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. Methods Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery ( n  = 259) and validation ( n  = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives ( n  = 15), were measured using mass spectrometry (MS). Results The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-Methoxyestrone were associated with an increased risk of development of metastasis/deaths. Conclusions Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-Methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.

  • Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression.
    British journal of cancer, 2021
    Co-Authors: Jean-philippe Emond, Louis Lacombe, Patrick Caron, Véronique Turcotte, David Simonyan, Armen Aprikian, Fred Saad, Michel Carmel, Simone Chevalier, Chantal Guillemette
    Abstract:

    Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery (n = 259) and validation (n = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives (n = 15), were measured using mass spectrometry (MS). The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-Methoxyestrone were associated with an increased risk of development of metastasis/deaths. Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-Methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.

Herman Adlercreutz - One of the best experts on this subject based on the ideXlab platform.

  • urinary phytoestrogen excretion of rats bearing methylnitrosourea induced mammary carcinoma in response to treatment with 2 methoxyestradiol
    The Journal of Steroid Biochemistry and Molecular Biology, 2007
    Co-Authors: T H Lippert, Herman Adlercreutz, M R Berger, H Seeger, Alfred O. Mueck
    Abstract:

    Abstract The effect of treating mammary tumor-bearing rats with 2-methoxyestradiol (2-MeE2) on the urinary excretion of 12 phytoestrogens was investigated and compared with the changes in urinary excretion of estradiol metabolites. Alterations of excretion were registered for isoflavonoids, lignans and coumestans. However, due to large variations statistical significant differences were found only for two lignans, i.e. significant increases of enterodiol and matairesinol. Since the single components of phytoestrogens showed diverse alterations, excretions were expressed also by the ratio of total isoflavonoids to total lignans and compared with the estrogen ratios 2-hydroxyestrone to 16α-hydroxyestrone and A-ring to D-ring metabolites. The ratio of isoflavonoids to lignans was consistently decreased, whereas both ratios of estradiol metabolites were highly increased. The latter effect is probably due to demethylation of 2-Methoxyestrone resulting in high catechol estrogen levels in urine. These results suggest that the high levels of catechol estrogens, produced by 2-MeE2 treatment, may have influenced the urinary excretion pattern of phytoestrogens.

  • Catecholestrogens excretion in smoking and non-smoking postmenopausal women receiving estrogen replacement therapy.
    The Journal of Steroid Biochemistry and Molecular Biology, 2000
    Co-Authors: Lev M. Berstein, Olga S. Kolesnik, Vera B. Gamajunova, Herman Adlercreutz
    Abstract:

    Abstract Estrogens are involved in the etiology of breast cancer. Their blastomogenic influence may be partly realized through their conversion into catecholestrogens, rate of which may be modified by smoking. The risk of having breast cancer diagnosed can increase in women using estrogen replacement therapy (ERT). The principal aim of this investigation was to compare the excretion of classical estrogens and catecholestrogens in smoking and non-smoking postmenopausal women receiving Progynova (estradiol valerate, 2 mg/day, 1 month). Total 16 women were studied before and after treatment. Urinary estrogen profile method based on isotope dilution capillary gas chromatography–mass spectrometry was used. Before ERT, significantly lower excretion of 16-epiestriol and 4-hydroxyestrone (4-OHE1) and lower ratio of 4-OHE1/E1 were revealed in smokers. After ERT, much higher excretion of 2-OHE1, and 4-hydroxyestradiol (4-OHE2), higher ratios of 2-OHE1/E1 and 4-OHE1/E1 and lower ratio of 2-Methoxyestrone/2-OHE1 were discovered in smokers as compared to non-smoking women. In conclusion only combination of ERT + smoking and not smoking itself leads to the specific prevalence of catecholestrogens (2-OH- and carcinogenic and DNA-damaging 4-OH-metabolites) that may increase risk of genotoxic variant of hormone-induced breast carcinogenesis without influence on the total morbidity.

Louis Lacombe - One of the best experts on this subject based on the ideXlab platform.

  • Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression
    British Journal of Cancer, 2021
    Co-Authors: Jean-philippe Emond, Louis Lacombe, Patrick Caron, Véronique Turcotte, David Simonyan, Armen Aprikian, Fred Saad, Michel Carmel, Simone Chevalier, Chantal Guillemette
    Abstract:

    Background Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. Methods Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery ( n  = 259) and validation ( n  = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives ( n  = 15), were measured using mass spectrometry (MS). Results The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-Methoxyestrone were associated with an increased risk of development of metastasis/deaths. Conclusions Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-Methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.

  • Urinary oestrogen steroidome as an indicator of the risk of localised prostate cancer progression.
    British journal of cancer, 2021
    Co-Authors: Jean-philippe Emond, Louis Lacombe, Patrick Caron, Véronique Turcotte, David Simonyan, Armen Aprikian, Fred Saad, Michel Carmel, Simone Chevalier, Chantal Guillemette
    Abstract:

    Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery (n = 259) and validation (n = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives (n = 15), were measured using mass spectrometry (MS). The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-Methoxyestrone were associated with an increased risk of development of metastasis/deaths. Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-Methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.