科研之友
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摘要
Selective estrogen receptor modulators and a combination of mechanistically distinct chemotherapeutic agents represent conventional therapeutic interventions for estrogen receptor-positive (ER+) clinical breast cancer. Longterm treatment with these agents is associated with acquired tumor resistance and other adverse side effects that impact on patient compliance. Herbal medicines are being widely used in complementary and alternative medicine. However, long-term safety and efficacy of the use of herbal medicines, as well as their interaction with conventional endocrine and chemotherapeutic drug regimens remain largely unknown. The present study utilized a human cell culture model for ER+ clinical breast cancer to examine the potential therapeutic efficacy of an aqueous extract prepared from the fruit of popular Chinese herb Cornus officinalis (CO), also known as Fructus cornii. The human mammary carcinoma-derived MCF-7 cell line represented the model. Status of anchorage-independent growth and cellular metabolism of 17 beta-estradiol (E-2) represented the quantitative end-point biomarkers for efficacy. MCF-7 cells adapted for growth in serum-depleted medium (0.7% serum, <1 nM E-2) retained their endocrine responsiveness as evidenced by growth promotion by physiological levels of E-2, and growth inhibition by the selective ER modulator tamoxifen at the clinically achievable concentrations.Treatnnent of MCF-7 cells with CO resulted in inhibition of E-2-stimulated growth in a dose-dependent manner. Similarly, CO treatment also produced a dose-dependent progressive reduction in the number of anchorage-independent colonies, indicating effective reduction of the carcinogenic risk. Treatment of MCF-7 cells with CO at a maximally effective cytostatic concentration resulted in a 5.1-fold increase in the formation of the anti-prolifertive E-2 metabolite 2-hydoxyestrone (2-OHE1), a 63.6% decrease in the formation of the pro-mitogenic metabolite 16 alpha-hydroxestrone (16-alpha OHE1) and a 9.1% decrease in the formation of mitogenically inert metabolite estrone (E-3). These alterations led to a 14.5-fold increase in the 2-OHE1:16 alpha-OHE1, and a 3.3-fold increase in the E-3:16 alpha-OHE1 ratios. These data validate a rapid cell culture-based mechanistic approach to prioritize efficacious herbal medicinal products for long-term animal studies and future clinical trials on ER+ clinical breast cancer.
- 出版日期2012-1
