Abstract 2606: Chemo-preventive efficacy of a natural product anti-cancer agent which surpasses Taxol

Breast cancer (BC), a major public health problem, is one of the leading causes of cancer-related deaths among women. In particular, triple-negative breast cancer (TNBC), the most aggressive form of BC poses significant therapeutic challenges. TNBCs are most common in women with BRCA1 gene mutations, younger women, and in pre-menopausal African American (AA) women compared to White women, significantly contributing to health disparities. Consisting of many heterogeneous, undifferentiated cell types including very high mammary cancer stem cell (MCSCs) content, TNBCs are diseases with high recurrence rates. Combining therapeutics to target a variety of growth pathways has inhibited growth and shrunk aggressive TN tumors. Yet, a major drawback of such therapy is the severe side effects commonly used chemotherapeutic agents have on normal cells. Therefore there is a critical need to develop new combinations of therapeutics that target MCSCs and improve the anticancer effects, while reducing harmful side effects. We present compelling preliminary findings comparing the anticancer effects of aqueous extracts of a plant, Vernonia amygdalina (VA), alone or in combination with Paclitaxel (TAX) in vitro and against TNBC cells injected into athymic mice intra-peritoneally. The effects of TAX alone or VA extracts alone or with TAX, were evaluated in Hsd:Athymic Nude-Foxn1nu, age 5-6 weeks, female mice inoculated subcutaneously with Hras MCSCs. Animals were grouped as follows: 1-Control, inoculated with Hras cells only; 2-VA treatment (10 mg/kg) simultaneously with injection of Hras cells, followed by 16-day VA treatment; 3-replicate of 2; 4-pretreatment with VA 10 days before injection of Hras cells, followed by 16-day VA treatment; 5-IP inoculation of TAX (10 mg/kg) simultaneously with injection of Hras cells; and 6-subcutaneous inoculation of VA (5 mg/kg) plus IP injection of TAX (5 mg/kg) simultaneously with injection of Hras cells. Studies revealed that though there was a lag in tumor growth for all treatment groups, the most significant reduction in tumor size was observed in group 4 animals, those which had been pretreated with VA each day for 10 days prior to inoculation with Hras cells. In the second round of experiments, we evaluated the efficacy of VA extracts (10-day pretreatment, high dose, 20 mg/kg) administered simultaneously with injections of both Hras cells and AA woman-derived MDA-MB-468 cells, at opposing sites, versus combined treatment with very low doses of VA and TAX (5 mg/kg of each agent, subcutaneously) toward inhibition of growth of tumors in our nude mice model. Based upon our findings, VA extract exhibits chemopreventative efficacy, addressing a major health problem which is the dominant biological cause of population-based disparities in BC mortality in the U.S. Our expectation is that this work could direct further in vivo studies and eventually translate to human clinical trials. Citation Format: Carolyn B. Howard. Chemo-preventive efficacy of a natural product anti-cancer agent which surpasses Taxol. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2606.