P3-09-04: Comparative Preventive Efficacy of Aqueous Extracts from Lycium Barbarum Bark and Fruit on Estrogen Receptor Positive Human Mammary Carcinoma MCF-7 Cells.
Authors: NT Telang, G Li, DW Sepkovic, LH Bradlow, GGY Wong, NT Telang
Journal: Cancer Research (2011)

Abstract Background: Chemotherapy, selective estrogen receptor modulators and aromatase inhibitors represent major treatment options for estrogen receptor positive (ER+) clinical breast cancer. These modalities frequently exhibit acquired tumor resistance and adverse systemic toxicity. Natural herbs are increasingly being used in the integrative support of breast cancer patients undergoing conventional treatment modalities and for prevention purposes. We previously reported favorable findings for the fruit of Lycium barbarum (LB), known commonly as goji berry, in the prevention for ER+ breast cancer (Nutrition &amp; Cancer 61:408–414, 2009). The present study compares the preventive efficacy of non-fractionated aqueous extracts from the bark of LB (LBB) and the fruit of LB (LBF) on a cell culture model for ER + breast cancer. Material and Methods: The ER+ human mammary carcinoma derived MCF-7 cells represented the model. Anchorage dependent growth, anchorage independent colony formation and cellular metabolism of 17β-estradiol (E2) represented the mechanistic bases for efficacy. Results: MCF-7 cells grown in serum depleted medium retained their responsiveness to E2, exhibiting E2 stimulated promotion of anchorage dependent growth and anchorage independent colonies. LBB was much more potent than LBF as evidenced by a 95% reduction of IC50 from 0.38% for LBF to 0.02% for LBB, and a 95% reduction of maximum cytostatic concentration (MCC) from 1% for LBF to 0.05% for LBB. At their respective MCC, LBB treatment and LBF treatment produced a 93% and an 89% decrease, respectively, in the number of anchorage independent colonies. Also, LBB produced a 6.8 fold increase in 2-hydroxyestrone (2-OHE1), a 40% decrease in 16a-hydroxyestrone (16a-OHE1) and a 3.7 fold increase in estriol (E3) formation. The corresponding values for LBF were 3.9, 33 and 10.5. LBB treatment resulted in a 16.3 fold increase in 2-OHE1:16a-OHE1 ratio and a 2 fold increase in E3:16a-OHE1 ratio, while LBF treatment produced a 6.0 fold increase and a 2.9 fold increase, respectively, in these endocrine biomarkers. These data suggest that the preventive efficacy of LBB may predominantly be due to up-regulation of the anti-proliferative 2-OHE1 formation, while accelerated conversion of the pro-mitogenic 16α-OHE1 to the mitogenically inert E3 is the case with LBF. Discussion: Growth inhibitory profiles of LBB and LBF may in part be due to their distinct chemical composition and their complementary actions on E2 metabolism. The superior sensitivity of LBB relative to LBF, together with its non-toxic nature, suggests the feasibility of its use in the prevention of human breast cancer. A prevention trial to assess its efficacy and to establish relevant dose schedule is warranted. This study validates a mechanism based approach to identify and prioritize efficacious herbal extracts for the prevention of ER+ breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-09-04.