Abstract P4-13-04: Efficacy of dipsacus asperoides (DA) in a model for triple negative breast cancer

Abstract

Abstract Background: The triple negative breast cancer (TNBC) is characterized by the absence of estrogen receptor-α (ER-α), Progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2). This molecular subtype responds only to conventional cytotoxic chemotherapy and to small molecule based targeted therapy. These therapeutic options are associated with long-term systemic toxicity and acquired tumor resistance leading to compromised efficacy. These limitations emphasize identification of efficacious non-toxic agents for secondary prevention/therapy of TNBC. Dipsacus asperoides (DA) is a Chinese herb of a nutritional nature. The root of this herb represents an ingredient that is commonly included in the traditional Chinese herbal formulations for health management purposes. The present study examines the growth inhibitory effects of DA and identifies possible mechanistic leads for their efficacy in a preclinical cell culture model for TNBC. Experimental Model, Herbal Extract and Biomarkers: The human mammary carcinoma derived ER-α -, PR - and HER-2 - MDA-MB-231 cell linerepresents the model for TNBC. Non-fractionated aqueous extract from DA represents the test agent. Anchorage dependent growth, anchorage independent (AI) colony formation, cell cycle progression and relevant pathway specific mechanistic assays represent the quantitative biomarkers for efficacy. Results: Treatment of MDA-MB-231 cells with DA extract induces a dose dependent cytostatic growth arrest (IC50: 0.0015%, IC90: 0.0030%), and strongly inhibits AI colony formation. Within the cytostatic concentration range, DA treatment inhibits cell cycle progression via progressive G2/M arrest, suggesting abrogation of the G2/M checkpoint affecting DNA damage repair pathway. The induction of cellular apoptosis by DA is indicated by a dose dependent up-regulation of pro-apoptotic Caspase 3/7 activity. Conclusion: These data identify potential mechanistic leads for the efficacy of DA in the present model. The present study validates a mechanism based approach to prioritize efficacious non-toxic herbal extracts for secondary prevention/therapy of the TNBC molecular subtype of clinical breast cancer. Citation Format: Telang NT, Nair HB, Wong GYC. Efficacy of dipsacus asperoides (DA) in a model for triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-13-04.