Nutritional Herbs Research Articles

Abstract P1-10-02: Comparative Preventive Efficacy of Select Chinese Herbs in Breast Carcinoma Derived Isogenic Cells with Modulated Estrogen Receptor Functions

Abstract Background: Human mammary carcinoma derived estrogen receptor positive (ER+) MCF-7 cells depend on 17β-estradiol (E2) for cellular proliferation in vitro and for tumor development in vivo. Traditionally, ER functions as a ligand activated nuclear transcription factor with E2 as its physiological ligand, and limited availability of E2 modulates ER functions. We have recently demonstrated preventive efficacy of selected Chinese nutritional herbs in this MCF-7 cell culture model. The present study screened additional Chinese nutritional herbs for their preferential preventive efficacy on MCF-7 cells with modulated ER functions. Methods: MCF-7 cells were maintained in medium supplemented with either 0.7% serum, <1 nM E2, or 0.7% serum+20 nM E2. This approach, while preserving the MCF-7 genotype, provides isogenic cells with either non-functional ER (ER-NF) or functional ER (ER-F) phenotype, and thereby, enables paired comparisons for the preventive efficacy of herbs on the two phenotypes. Anchorage dependent and anchorage independent growth, cell cycle progression, cellular apoptosis, and E2 metabolism represent the quantitative end points.Results: Long-term maintenance of MCF-7 cells in a serum-depleted culture medium (0.7% serum, < 1 nM E2) selects a proliferative sub-population of E2 responsive cells with transiently non-functional ER due to limited availability of E2. The growth inhibitory effects of non-fractionated aqueous extracts from 15 Chinese nutritional herbs were compared in MCF-7 cells selected for either the ER-NF or the ER-F phenotype. Comparative dose response experiments identified IC50 concentrations, and thereby, facilitated rank ordering for growth inhibition. Although all the herbs tested were effective in the present model, two herbs exhibited greater efficacy for the ER-NF phenotype, eight herbs exhibited greater efficacy for the ER-F phenotype, while five herbs exhibited equal efficacy for both the ER-NF and the ER-F phenotypes. Representative herbs at their respective maximum cytostatic concentrations from these three groups, inhibited anchorage independent growth, induced G1 arrest, induced apoptosis, and regulated E2 metabolism in favor of the anti-proliferative metabolites 2-hydroxyestrone and estriol. Conclusions: Preferential growth inhibition by Chinese nutritional herbs in isogenic ER-NF and ER-F phenotypes of MCF-7 cells and mechanistic efficacy of representative herbs identify possible leads towards their rapid prioritization for planning prevention trials on ER+ and ER− clinical breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-10-02.

Abstract P1-06-03: Chinese Herb Fructus Cornii Exhibits Preventive Efficacy in a Cell Culture Model for Hormone Responsive Breast Cancer

Abstract Background: Selective estrogen receptor modulators and combination of chemotherapeutic agents represent conventional therapeutic interventional strategies for estrogen receptor positive (ER+) clinical breast cancer. Herbal medicines have been extensively used in alternative and complementary medicine for cancer of various organ sites. Concerns of adverse toxicity or acquired tumor resistance from conventional chemo-endocrine therapy, rationalizes the use of herbal medicines independently or in combination with chemo-endocrine therapy. The present study has utilized a human cell culture model for ER+ breast cancer to assess potential preventive efficacy of a popular Chinese nutritional herb Fructus Cornii (FC). Material and Methods: The ER+ human mammary carcinoma derived MCF-7 cells represented the model. Status of cellular metabolism of estradiol (E2), anchorage dependent growth and anchorage independent colony formation provided the quantitative end point biomarkers for efficacy. Results: MCF-7 cells maintained in a serum depleted medium (E2<1 nM) retained E2 responsiveness as evidenced by growth modulation by E2, its metabolites, anti-estrogen Tamoxifen, and by the persistence of E2 metabolism via the C17-oxidation, C2-hydroxylation and C16α-hydroxylation pathways. Treatment of E2 stimulated MCF-7 cells with FC produced cytostatic growth arrest and reduction in the number of anchorage independent colonies in a dose dependent manner. Treatment of MCF-7 cells with FC at the maximum cytostatic concentration increased anti-mitogenic 2-hydroxyestrone (2-OHE1), and decreased pro-mitogenic 16α-hydroxyestrone (16α-OHE1) formation. Discussion: These data identify a mechanistic lead for the efficacy of FC and thereby, validate a human cell culture based approach for rapid prioritization of efficacious herbal medicinal products for prevention/therapy of ER+ clinical breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-06-03.