Growth Inhibitory Efficacy of Tabebuia Avellanedae in a Model for Triple Negative Breast Cancer

Abstract

Background: Tabebuia avellanedae (TA) is a tree that is indigenous to the Amazon rainforest. The experiments in the present study were designed to examine the inhibitory effects of TA, and to identify mechanistic targets for its efficacy in the estrogen-α receptor (ER-α), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) negative MDA-MB-231 model for triple negative breast cancer (TNBC). Methods: Non-fractionated aqueous extract from the inner bark of TA was used in the experiments. Anchorage dependent growth, anchorage independent (AI) colony formation, cell cycle progression, and expressions of relevant regulatory proteins represented quantitative end points. Results: Long-term treatment for 21 days with the maximum cytostatic concentration of 2.5% TA resulted in a 90% inhibition (P=0.014) in AI colony number. Short-term treatment for 2 days with 1.0% TA (IC50) resulted in about a 1.3 fold increase (P=0.014) in G1: S+G2/M ratio, about a 1.48 fold increase (P=0.010) in the sub G0 (apoptotic) cells and about a 3.2 fold increase (P=0.014) in the pro-apoptotic caspase 3/7 activity. Mechanistically, the short-term treatment with 2.5% TA decreased Cyclin D1 expression by about 83.3%, and pRB expression by about 73.3%. Conclusion: TNBC represents an aggressive cancer notable for its resistance to conventional and targeted therapy. Non-toxic natural substances may represent testable alternatives. This study identifies potential mechanistic leads for TA as a novel naturally occurring testable alternative for secondary prevention/therapy of TNBC, and validates a novel mechanistic approach to evaluate efficacious non-toxic phytochemicals and herbs as testable alternatives against therapy resistant breast cancer.