脱氢表雄酮(青春素,DHEA)是一种天然激素,它在人体内的产生会随着衰老而减少。作为非处方药,男性服用DHEA是因为它有抗衰老作用,或者说它在体内代谢后会生成雄性激素。饮食中异黄酮摄入量的增加会降低前列腺癌发病危险。
红三叶草是异黄酮的来源之一。DHEA和异黄酮这两种补充剂对前列腺都能发挥激素作用,但对它们的安全性还缺乏了解。美国癌症研究会杂志《癌症预防研究》最近发表的一项研究报告说,可以在实验室对细胞的DHEA水平进行调解,以了解它的作用。
美国国家卫生研究院全国补充与替代医学中心的科学家朱莉娅﹒阿诺德博士说,许多男性和女性从健康出发根据网上找到的信息为自己开药,面对这种情况,我们还需做更多研究来评估这些补充剂的安全性。
为此,中心实验室对培养的前列腺癌细胞和它的基质细胞之间所发信号作了研究。“DHEA对前列腺组织的作用依赖于这两种细胞之间‘交谈’,进一步说,对含有炎症或早期癌症损伤的组织是有害的,因为这些细胞可诱导DHEA形成更多的雄性激素。” 阿诺德说。
DHEA与转化生长因子β-1结合后,基质细胞产生的睾丸素和前列腺特异性抗原蛋白的分泌会增加2-4倍,癌细胞的基因表达增加50倍。当在这些培养细胞中加入三叶草异黄酮后,DHEA产生雄性激素作用会受到抑制。
“在前列腺微环境中所发生这些变化说明,三叶草异黄酮有潜在的癌症预防作用。” 阿诺德说。
红三叶草异黄酮可以改变前列腺中雄激素的作用,但还需要更多的实验室和临床研究来证实这些作用。
这项实验室研究让科学家进一步了解了前列腺的生物学基础,也认识了DHEA和红三叶植物的细胞和分子机制。阿诺德说,中心将进一步对DHEA和其他补充剂进行研究,以找到一些癌症预防办法。(生物谷Bioon.com)
生物谷推荐原始出处:
Cancer Prevention Research, February 1, 2009.doi: 10.1158/1940-6207.CAPR-08-0062
Endocrine-Immune-Paracrine Interactions in Prostate Cells as Targeted by Phytomedicines
Nora E. Gray, Xunxian Liu, Renee Choi, Marc R. Blackman and Julia T. Arnold
Authors' Affiliation: Endocrine Section, Laboratory of Clinical Investigation, Division of Intramural Research, National Center for Complementary and Alternative Medicine, NIH, Bethesda, Maryland
Requests for reprints: Julia T. Arnold, Endocrine Section, Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, Building 10, Room 2B47, 9000 Rockville Pike, Bethesda, MD 20892-1547.
Dehydroepiandrosterone (DHEA) is used as a dietary supplement and can be metabolized to androgens and/or estrogens in the prostate. We investigated the hypothesis that DHEA metabolism may be increased in a reactive prostate stroma environment in the presence of proinflammatory cytokines such as transforming growth factor β1 (TGFβ1), and further, whether red clover extract, which contains a variety of compounds including isoflavones, can reverse this effect. LAPC-4 prostate cancer cells were grown in coculture with prostate stromal cells (6S) and treated with DHEA +/– TGFβ1 or interleukin-6. Prostate-specific antigen (PSA) expression and testosterone secretion in LAPC-4/6S cocultures were compared with those in monocultured epithelial and stromal cells by real-time PCR and/or ELISA. Combined administration of TGFβ1 + DHEA to cocultures increased PSA protein secretion two to four times, and PSA gene expression up to 50-fold. DHEA + TGFβ1 also increased coculture production of testosterone over DHEA treatment alone. Red clover isoflavone treatment led to a dose-dependent decrease in PSA protein and gene expression and testosterone metabolism induced by TGFβ1 + DHEA in prostate LAPC-4/6S cocultures. In this coculture model of endocrine-immune-paracrine interactions in the prostate, TGFβ1 greatly increased stromal-mediated DHEA effects on testosterone production and epithelial cell PSA production, whereas red clover isoflavones reversed these effects.