Effect of medicinal botanicals in breast cancer cell lines with different estrogen receptor expression
Authors: Frank D. Houghton, Mary S. Elm, Patricia K. Eagon
Journal: Cancer Research (2005)

5786  Several traditional Chinese medicines (TCM) are used to stimulate the immune system, in order to maintain health and as an adjuvant to chemotherapy. Previous work has shown that certain medicinal botanicals traditionally used for gynecological complaints have estrogenic properties, likely because of phytoestrogen content. The aims of this study were to examine if certain TCM herbs altered proliferation in breast cancer cells that are estrogen receptor (ER)-positive but differ in the expression of ERα and ERβ, and if these herbs altered cellular response to estradiol (E2). The cell lines MCF-7 (60:40 ERα:ERβ) and T47D (33:67 ERα:ERβ) were treated with various dilutions of standard extracts of dang gui (DG, angelica), ling zhi (LZ, reishi mushroom), gang cao (GC, licorice), he show wu (HSW, fo-ti), huang qi (HQ, astragalus) in the presence or absence of E2 (1nm). Controls were E2 treatment only and no treatment. After 72 hours, proliferation index was determined via a standard assay; values for herbal treatments were compared to those of controls. The two cell lines differed in response to E2, in that MCF-7 responded more strongly to E2 than did T47D (1.99 vs. 1.70). The most noteworthy difference between these two cell lines was seen in their responses to HSW, LZ, and DG. MCF-7 either had no response (HSW) or a slight response (DG and LZ) to these herbal extracts. T47D, on the other hand, exhibited a dose-related increase in proliferation at higher doses of HSW, LZ and DG, with DG and LZ exceeding the E2 control levels. This differential response was also seen when both cell lines were treated with these herbs along with E2. In MCF-7, E2 tended to mask the effects, if any, of these herbs. In contrast, in T47D cells, addition of E2 to both LZ and DG produced an additive effect, with proliferation index exceeding E2 levels at the higher doses. HSW with E2 in T47D cells had no effect on E2-induced proliferation. HQ alone was biphasic in both cell lines, with proliferative effects at highest doses reaching E2 control levels in MCF-7 and exceeding E2 control values in T47D. HQ with E2 had no effect on the E2-induced proliferation in MCF-7; however, in T47D cells, it maintained a biphasic response with enhancement of proliferation at higher doses. GC alone exhibited a proliferative effect equivalent to that of the E2 control in MCF-7; in T47D, GC produced a strong dose response exceeding that of the E2 control. These responses did not change with the addition of E2 to GC for both cell lines.These results indicate that TCM herbs used for immune system support may be estrogenic, and that the response differs depending on the cell line and the presence or absence of E2. In general, T47D cells are better responders to these herbs, most likely because of their higher content of ERβ, which has a higher affinity than ERα for phytoestrogens. The estrogenicity of these herbal preparations should be taken into account by those who want to reduce their estrogen exposure.