Abstract 1855: Re-purposing traditional Chinese anti-asthma formula ASHMI for triple negative breast cancer

Abstract

Abstract Breast cancer is the most common cancer among women worldwide, contributing to 25.4% of newly diagnosed cancer cases in 2018. Triple negative breast cancer (TNBC) accounts for 10-20% of the breast cancer cases and represents an unmet clinical need because of its higher risk of recurrence and metastasis. Adjuvant therapies have often been employed to prevent secondary recurrence. Traditional Chinese medicine (TCM) formulations have long been used in prevention and cure of many types of diseases because of its anti-inflammatory property. Mainstream treatment modalities for TNBC involve surgery, radiation and chemotherapy (adjuvant or neoadjuvant). Unfortunately, chemotherapy in these patients often lead to resistance, which underscores the importance of alternative therapeutic approaches for this cancer. To this end, we wanted to evaluate anti-carcinogenic property of a TCM formulation ASHMITM developed primarily for asthma treatment. ASHMI™ is an extract of 3 traditional Chinese medicinal herbs-Ganoderma lucidum (Ling-Zhi), Sophora flavescens Ait (Ku-Shen) and Glycyrrhiza uralensis Fischer (Gan-Gao). For this study, triple-negative/basal B mammary carcinoma cell line MDA-MB157 was treated with two different concentrations of ASHMI and cellular proliferation was examined by [3H] thymidine incorporation assay. ASHMITM treated cells showed approximately 74% less [3H] thymidine incorporation indicating dampened proliferation. This observation was validated using western blot analysis with whole cell lysate, showing reduced expression of proliferation markers PCNA and NFκB. Interestingly, an increased expression of tumor suppressor protein cyclin-dependent kinase inhibitor 1 C (p57, Kip2) was observed after ASHMITM treatment. Next, we tested anti-proliferative property of the individual constituents and observed Ganoderma lucidum (GL) extract had a comparable efficacy as the whole formulation at a concentration of 100μg/ml. This observation was further confirmed by western blot and the same expression pattern was observed for PCNA, NFκB and p57. GL was further fractionated into 11 sub-components and each component was tested for the their anti-proliferative activity using similar assays. Fraction 2 with Ganoderenic acid D showed dose-dependent inhibition of cell proliferation and was further tested for its activity at lower concentrations. Ganoderenic acid D had similar efficiency as 100μg/ml of whole GL extract at a concentration as low as 2.5μg/ml suggesting this active compound might be primarily responsible for the anti-proliferative effect of GL. Our studies using an anti-inflammatory formulation of TCM have identified an active anti-carcinogenic compound, Ganoderenic acid D, that could be potentially used as an adjuvant in TNBC therapies. Citation Format: Sanjukta Chakraborty, Fei Mo, Martin Walsh, Changda Liu, Mingzhuo Cou, Rachana Maniyar, Ghada Ben Rahoma, Sarnath Singh, Tara Jarboe, Michelle Carnazza, Raj Tiwari, Xiu-min Li. Re-purposing traditional Chinese anti-asthma formula ASHMI for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1855.