Abstract P5-14-02: Efficacy of tabebuia avellandae extract on a cell culture model for triple negative breast cancer

Abstract

Abstract Background: The triple negative breast cancer (TNBC), a molecular subtype of clinical breast cancer consisting of epithelial cells that lack estrogen receptor-α (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) expression, is non-responsive to either endocrine therapy or HER-2 targeted therapy. Chemotherapy is frequently associated with long-term systemic toxicity, acquired tumor resistance and resultant compromised treatment efficacy. These aspects emphasize a need to identify efficacious non-toxic agents for secondary prevention/therapy of TNBC. Non-fractionated aqueous extract from the inner bark of the Tabebuia avellandae (TA) tree found in the Amazon rainforest, available as a dietary supplement under the name of Taheebo or Pau d’arco, has documented efficacy in a cell culture model for the Luminal A breast cancer subtype, as well as for several other cancers. Present study examines the inhibitory effects of the TA extract, and identifies possible mechanistic targets for its efficacy in a cell culture model for TNBC. Nutritional Supplement, Experimental Model and Biomarkers: Lyophilized powder of non-fractionated TA extract from Taheebo Japan, Osaka, Japan, provides the source material for the study. The ER-/PR-/HER-2- MDA-MB-231 cell line represents the cell culture model for TNBC. Anchorage dependent growth, cell cycle progression, status of cell cycle regulatory proteins and anchorage independent colony formation, represent the quantitative biomarkers for efficacy. Results: Relative to the non-tumorigenic 184-B5 human mammary epithelial cells, the tumor derived MDA-MB-231 cells exhibited decreased population doubling time, increased saturation density, decreased G1: S+G2/M ratio and increased S+G2/M: Sub G0 ratio, indicating loss of homeostatic growth control. Additionally, unlike 184-B5 cells, MDA-MB-231 cells exhibited increased anchorage independent growth in vitro and tumor development in vivo, indicating enhanced cancer risk. Treatment of MDA-MB-231 cells with TA resulted in a substantial dose dependent cytostatic growth arrest (IC50:1.0%; IC90: 2.5%). Cell cycle analysis of TA treated cells revealed G1 arrest, leading to a progressive dose dependent increase in the G1: S+G2/M ratio. Mechanistically, TA decreased Cyclin D1 expression and attenuated RB phosphorylation, predicting Cyclin D-CDK4-pRB pathway as a molecular target for efficacy. Furthermore, TA effectively inhibited anchorage independent growth in a dose dependent manner. Conclusions: Present data demonstrated pronounced efficacy of TA as a naturally occurring nutritional substance in a cell culture model for TNBC, and validated TA as a promising non-toxic natural agent for secondary prevention/therapy of clinical TNBC. Citation Format: Nitin T Telang, Hareesh B Nair, George YC Wong. Efficacy of tabebuia avellandae extract on a cell culture model for triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-14-02.