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    ANTIESTROGENIC GLYCEOLLINS SUPPRESS HUMAN BREAST AND OVARIAN CARCINOMA PROLIFERATION AND TUMORIGENESIS
    3.
    发明申请
    ANTIESTROGENIC GLYCEOLLINS SUPPRESS HUMAN BREAST AND OVARIAN CARCINOMA PROLIFERATION AND TUMORIGENESIS 审中-公开

    公开(公告)号：WO2006118871A3

    公开(公告)日：2006-11-09

    申请号：PCT/US2006/015637

    申请日：2006-04-24

    申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF AGRICULTURE ,  TULANE CENTER FOR BIOENVIRONMENTAL RESEARCH ,  CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

    发明人： CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

    IPC分类号： A01N65/00

    摘要： The flavonoid family of phytochemicals, particularly those derived from soy, has received attention regarding their hormonal activity and their effects on human health and disease. The types and amounts of these compounds in soy and other plants are controlled by both constitutive expression and stress-induced biosynthesis. The health benefits of soy may therefore be dependent upon the amounts of the various hormonally active phytochemicals present. We have identified increased biosynthesis of the isoflavonoid phytoalexin compounds, Glyceollins I, Il and III, in soy plants grown under stressed conditions (elicited soy), which exhibit marked anti-estrogenic effects on ER function. Here we demonstrate that specific glyceollins, isolated from elicited soy, displayed anti-estrogenic activity, suppressing basal and estrogen stimulated colony formation of ER-positive estrogen dependent breast cancer cells and inhibiting ER-dependent gene expression of progesterone receptor (PgR) and stromal derived factor-1 (SDFI/CXCL^). Examining the effects of glyceollin on in vivo tumor formation/growth we demonstrate the ability of glyceollins to significantly suppress basal and estrogen-stimulated tumor growth of ER-positive MCF-7 breast and BG-1 ovarian carcinoma cells in ovariectomized female nude mice. We further demonstrate that the effects of glyceollins on suppression of tumor growth correlate with inhibition of estrogen stimulated PgR expression. In contrast to the uterotropic activity of tamoxifen the glyceollins displayed no uterine agonist activity. The Glyceollin (l-lll) compounds may represent an important component of the health effects of soy as well as represent novel anti-estrogens useful in the prevention or treatment of breast and ovarian carcinoma.

    GLYCEOLLINS SUPPRESS ANDROGEN-RESPONSIVE PROSTATE CANCER
    6.
    发明申请
    GLYCEOLLINS SUPPRESS ANDROGEN-RESPONSIVE PROSTATE CANCER 审中-公开
    谷氨酸激酶抑制剂和反应性前列腺癌

    公开(公告)号：WO2010075418A2

    公开(公告)日：2010-07-01

    申请号：PCT/US2009069250

    申请日：2009-12-22

    申请人： UNIV TULANE ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  BUROW MATTHEW E ,  WANG THOMAS T Y

    发明人： CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  BUROW MATTHEW E ,  WANG THOMAS T Y

    IPC分类号： A61K31/35 ,  A61K31/353 ,  A61K36/48 ,  A61P35/00

    CPC分类号： A61K31/35 ,  A61K31/353

    摘要： The present disclosure demonstrates the molecular effects of glyceollins on human prostate cancer cell LNCaP to further elucidate its potential effects on prostate cancer prevention. The glyceollins inhibited LNCaP cell growth similar to that of the soy isofiavone genistein. The growth inhibitory effects of the glyceollins appeared to be due to an inhibition on Gl /S progression and correlated with an up-regulation of cyclin-dependent kinase inhibitor Al and Bl mRNA and protein levels. By contrast, genistein only up-regulates cyclin-dependent kinase inhibitor Al. In addition, glyceollin treatments led to down-regulated mRNA levels for androgen responsive genes. In contrast to genistein, this effect of glyceollins on androgen responsive genes appeared to be mediated through modulation of an estrogen- but not androgen-mediated pathway. Hence, the glyceollins exerted multiple effects on LNCaP cells that may be considered cancer preventive and the mechanisms of action appeared to be different from other soy-derived phytochemicals.

    摘要翻译： 本发明揭示了glyceollins对人前列腺癌细胞LNCaP的分子效应，以进一步阐明其对前列腺癌预防的潜在影响。 glyceollins抑制LNCaP细胞生长与大豆异黄酮染料木素相似。 glyceollins的生长抑制作用似乎是由于对Gl / S进程的抑制，并且与细胞周期蛋白依赖性激酶抑制剂Al和Bl mRNA和蛋白质水平的上调相关。 相比之下，染料木素只上调细胞周期蛋白依赖性激酶抑制剂Al。 此外，甘草素处理导致雄激素反应基因的下调mRNA水平。 与染料木素相反，血凝素对雄激素反应基因的这种影响似乎是通过调节雌激素而不是雄激素介导的途径来介导的。 因此，glyceollins对可能被认为是预防癌症的LNCaP细胞产生多重效应，并且其作用机制似乎与其他大豆衍生的植物化学物质不同。

    ANTIESTROGENIC GLYCEOLLINS SUPPRESS HUMAN BREAST AND OVARIAN CARCINOMA PROLIFERATION AND TUMORIGENESIS
    7.
    发明申请
    ANTIESTROGENIC GLYCEOLLINS SUPPRESS HUMAN BREAST AND OVARIAN CARCINOMA PROLIFERATION AND TUMORIGENESIS 审中-公开
    神经性GLYCEOLLINS抑制人乳腺癌和卵巢癌的增殖和肿瘤发生

    公开(公告)号：WO2006118871A2

    公开(公告)日：2006-11-09

    申请号：PCT/US2006015637

    申请日：2006-04-24

    申请人： US AGRICULTURE ,  TULANE CT FOR BIOENVIRONMENTAL ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

    发明人： CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

    IPC分类号： A61K38/16 ,  A61K31/353 ,  A61K36/48

    CPC分类号： A61K36/48

    摘要： The flavonoid family of phytochemicals, particularly those derived from soy, has received attention regarding their hormonal activity and their effects on human health and disease. The types and amounts of these compounds in soy and other plants are controlled by both constitutive expression and stress-induced biosynthesis. The health benefits of soy may therefore be dependent upon the amounts of the various hormonally active phytochemicals present. We have identified increased biosynthesis of the isoflavonoid phytoalexin compounds, Glyceollins I, Il and III, in soy plants grown under stressed conditions (elicited soy), which exhibit marked anti-estrogenic effects on ER function. Here we demonstrate that specific glyceollins, isolated from elicited soy, displayed anti-estrogenic activity, suppressing basal and estrogen stimulated colony formation of ER-positive estrogen dependent breast cancer cells and inhibiting ER-dependent gene expression of progesterone receptor (PgR) and stromal derived factor-1 (SDFI/CXCL^). Examining the effects of glyceollin on in vivo tumor formation/growth we demonstrate the ability of glyceollins to significantly suppress basal and estrogen-stimulated tumor growth of ER-positive MCF-7 breast and BG-1 ovarian carcinoma cells in ovariectomized female nude mice. We further demonstrate that the effects of glyceollins on suppression of tumor growth correlate with inhibition of estrogen stimulated PgR expression. In contrast to the uterotropic activity of tamoxifen the glyceollins displayed no uterine agonist activity. The Glyceollin (l-lll) compounds may represent an important component of the health effects of soy as well as represent novel anti-estrogens useful in the prevention or treatment of breast and ovarian carcinoma.

    摘要翻译： 植物化学成分的黄酮类化合物，特别是那些衍生自大豆的类黄酮，已经受到关于其激素活性及其对人类健康和疾病的影响的关注。 这些化合物在大豆和其他植物中的类型和数量都受到组成型表达和应激诱导的生物合成的控制。 因此，大豆的健康益处可能取决于存在的各种激素活性植物化学物质的量。 我们已经鉴定出在胁迫条件下生长的大豆植物（引发大豆）中异黄酮类植物抗坏血酸化合物Glyceollins I，II和III的生物合成的增加，其对ER功能表现出显着的抗雌激素作用。 在这里我们证明，从引出的大豆中分离的特定的果糖显示出抗雌激素活性，抑制ER阳性雌激素依赖性乳腺癌细胞的基础和雌激素刺激的集落形成，并抑制孕激素受体（PgR）和基质衍生的ER依赖性基因表达 因子-1（SDFI / CXCL ^）。 检查血糖浓度对体内肿瘤形成/生长的影响，我们证明了血清蛋白在卵巢切除的雌性裸鼠中显着抑制ER阳性MCF-7乳腺和BG-1卵巢癌细胞的基础和雌激素刺激的肿瘤生长的能力。 我们进一步证明，糖蛋白对抑制肿瘤生长的影响与抑制雌激素刺激的PgR表达有关。 与他莫昔芬的子宫活动相反，glyceollins不显示子宫激动剂活性。 Glyceollin（l-lll）化合物可能代表大豆健康影响的重要组成部分，也可代表可用于预防或治疗乳腺癌和卵巢癌的新型抗雌激素。