Extraction-dependent effects of American ginseng (Panax quinquefolium) on human breast cancer cell proliferation and estrogen receptor activation
Extraction-dependent effects of American ginseng (Panax quinquefolium) on human breast cancer cell proliferation and estrogen receptor activation
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DOI：
10.1177/1534735406291341
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发表时间：
2006-09-01
影响因子：
2.9
通讯作者：
Murphy, Laura L.
中科院分区：
文献类型：
--
作者：
King, Mandy L.;Adler, Stuart R.;Murphy, Laura L.
假设：人参根提取物和具有生物活性的人参皂甙已被证明可以抑制人类癌细胞系的增殖，包括乳腺癌。然而，有相互矛盾的数据表明人参提取物 (GE) 可能具有也可能不具有雌激素作用，这对于患有雌激素依赖性癌症的个体来说可能是禁忌的。目前的研究旨在解决以下假设：西洋参 (Panax quinquefolium) 根的提取方法将决定其使用雌激素受体 (ER) 阳性 MCF-7 人乳腺癌细胞模型产生雌激素反应的能力。方法：用宽浓度范围的甲醇（alc-GE）或水提取（w-GE）人参根处理 MCF-7 细胞 6 天。细胞在含有正常或活性炭剥离的胎牛血清的培养基中生长，以限制与外源雌激素的接触。因此，GE 增加的 MCF-7 细胞增殖表明潜在的雌激素作用。通过用 ER 拮抗剂 ICI 182,780 (1 nM) 和 4-羟基他莫昔芬 (0.1 μM) 阻断 GE 诱导的 MCF-7 细胞增殖证实了这一点。此外，还检查了 GE 结合 ER α 或 ER β 并刺激雌激素反应基因的能力。结果：当细胞维持在低雌激素条件下时，Alc-GE（而非 w-GE）能够在低浓度（5-100 μg/mL）下增加 MCF-7 细胞增殖。 alc-GE 对 MCF-7 细胞增殖的刺激作用被 ER 拮抗剂 ICI 182,780 或 4-羟基他莫昔芬阻断。在较高浓度的 GE 下，无论培养基条件如何，两种提取物都能抑制 MCF-7 和 ER 阴性 MDA-MB-231 细胞增殖。结合测定表明 alc-GE（而非 w-GE）能够结合 ER α 和 ER β。 Alc-GE (50 μg/mL) 还诱导雌激素反应性 pS2 基因的表达以及孕激素受体 (PgR) 基因表达增加约 2.5 倍，而 w-GE 则没有效果。结论：这些数据表明，低浓度的 alc-GE（而非 w-GE）会引起雌激素效应，证据是通过 ER 拮抗剂拮抗的方式增加 MCF-7 细胞增殖、alc-GE 与雌激素受体的相互作用以及 alc-GE 增加雌激素反应基因的表达。因此，不同实验室之间的结果差异可能是由于分析雌激素活性的 GE 类型所致。
Hypothesis: Ginseng root extracts and the biologically active ginsenosides have been shown to inhibit proliferation of human cancer cell lines, including breast cancer. However, there are conflicting data that suggest that ginseng extracts (GEs) may or may not have estrogenic action, which might be contraindicated in individuals with estrogen-dependent cancers. The current study was designed to address the hypothesis that the extraction method of American ginseng (Panax quinquefolium) root will dictate its ability to produce an estrogenic response using the estrogen receptor (ER)-positive MCF-7 human breast cancer cell model. Methods: MCF-7 cells were treated with a wide concentration range of either methanol- (alc-GE) or water-extracted (w-GE) ginseng root for 6 days. Cells were grown in media containing either normal or charcoal-stripped fetal calf serum to limit exposure to exogenous estrogen. Thus, an increase in MCF-7 cell proliferation by GE indicated potential estrogenicity. This was confirmed by blocking GE-induced MCF-7 cell proliferation with ER antagonists ICI 182,780 (1 nM) and 4-hydroxytamoxifen (0.1 mu M). Furthermore, the ability of GE to bind ER alpha or ER beta and stimulate estrogen-responsive genes was examined. Results: Alc-GE, but not w-GE, was able to increase MCF-7 cell proliferation at low concentrations (5-100 mu g/mL) when cells were maintained under low-estrogen conditions. The stimulatory effect of alc-GE on MCF-7 cell proliferation was blocked by the ER antagonists ICI 182,780 or 4-hydroxytamoxifen. At higher concentrations of GE, both extracts inhibited MCF-7 and ER-negative MDA-MB-231 cell proliferation regardless of media conditions. Binding assays demonstrated that alc-GE, but not w-GE, was able to bind ER alpha and ER beta. Alc-GE (50 mu g/mL) also induced an approximate 2.5-fold increase in expression of the estrogen-responsive pS2 gene, as well as progesterone receptor (PgR) gene expression, whereas w-GE was without effect. Conclusion: These data indicate that low concentrations of alc-GE, but not w-GE, elicit estrogenic effects, as evidenced by increased MCF-7 cell proliferation, in a manner antagonized by ER antagonists, interactions of alc-GE with estrogen receptors, and increased expression of estrogen-responsive genes by alc-GE. Thus, discrepant results between different laboratories may be due to the type of GE being analyzed for estrogenic activity.