Johnson Kailee A, Vemuri Sravan, Alsahafi Sameerh, Castillo Rudy, Cheriyath Venugopalan
a Department of Biological and Environmental Sciences , Texas A&M University-Commerce , Commerce , Texas , USA.
Nutr Cancer. 2016 May-Jun;68(4):622-33. doi: 10.1080/01635581.2016.1154578. Epub 2016 Apr 4.
Due to the association of hormone replacement therapy (HRT) with breast cancer risk, estrogenically active soy isoflavones are considered as an HRT alternative to alleviate menopausal symptoms. However, several recent reports challenged the health benefits of soy isoflavones and associated them with breast cancer promotion. While glyconic isoflavones are the major constituents of soybean seeds, due to their low cell permeability, they are considered to be biologically inactive. The glyconic isoflavones may exert their effects on membrane-bound estrogen receptors or could be converted to aglycones by extracellular β-glucosidases. Therefore, we hypothesized that despite their low cell permeability, soybean cultivars with high glyconic isoflavones may promote breast cancer cell growth. To test this, composition and estrogenic activity of isoflavones from 54 commercial soybean cultivars were determined. Soybean seeds produced in identical climate and growth conditions were used to minimize the effects of extraneous factors on isoflavone profile and concentrations. The glyconic daidzin concentration negatively correlated with genistin and with other aglycones. Relative to control, isoflavone extracts from 51 cultivars were estrogenic and promoted the growth of estrogen receptor positive (ER+) breast cancer cell line MCF-7 from 1.14 to 4.59 folds and other three cultivars slightly reduced the growth. Among these, extracts from three cultivars were highly estrogenic and promoted MCF-7 cell growth by 2.59-4.64 folds (P<0.005). Among six isoflavones, daidzin was positively associated with MCF-7 cell growth (P<0.005, r = 0.13966), whereas the negative correlation between genistin and MCF-7 cell growth was nearly significant (P≤0.0562, r = -0.026141). Furthermore, in drug interaction studies daidzin-rich isoflavone extracts antagonized tamoxifen, an ER inhibitor. Taken together, our results suggest that the glyconic daidzin-rich soy isoflavone extracts may exert estrogenic effects and promote ER+ breast cancer growth.
由于激素替代疗法（HRT）与乳腺癌风险相关，具有雌激素活性的大豆异黄酮被视为缓解更年期症状的HRT替代物。然而，最近的几份报告对大豆异黄酮的健康益处提出了质疑，并将其与促进乳腺癌联系起来。虽然糖苷型异黄酮是大豆种子的主要成分，但由于其细胞通透性低，它们被认为是无生物活性的。糖苷型异黄酮可能对膜结合雌激素受体发挥作用，或者可被细胞外β-葡萄糖苷酶转化为苷元。因此，我们推测，尽管糖苷型异黄酮的细胞通透性低，但富含糖苷型异黄酮的大豆品种可能促进乳腺癌细胞生长。为了验证这一点，我们测定了54个商业大豆品种中异黄酮的组成和雌激素活性。使用在相同气候和生长条件下生产的大豆种子，以尽量减少外部因素对异黄酮谱和浓度的影响。糖苷型黄豆苷浓度与染料木苷以及其他苷元呈负相关。相对于对照，51个品种的异黄酮提取物具有雌激素活性，可使雌激素受体阳性（ER+）乳腺癌细胞系MCF-7的生长提高1.14至4.59倍，其他三个品种则略微降低了其生长。其中，三个品种的提取物具有高度雌激素活性，可使MCF-7细胞生长提高2.59 - 4.64倍（P<0.005）。在六种异黄酮中，黄豆苷与MCF-7细胞生长呈正相关（P<0.005，r = 0.13966），而染料木苷与MCF-7细胞生长之间的负相关接近显著（P≤0.0562，r = -0.026141）。此外，在药物相互作用研究中，富含黄豆苷的异黄酮提取物拮抗了雌激素受体抑制剂他莫昔芬。综上所述，我们的结果表明，富含糖苷型黄豆苷的大豆异黄酮提取物可能发挥雌激素作用并促进ER+乳腺癌生长。
