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

Background: Tabebuia avellanedae (TA) is a tree that is indigenous to theAmazon rainforest. The experiments in the present study were designed toexamine the inhibitory effects of TA, and to identify mechanistic targets for itsefficacy in the estrogen-α receptor (ER-α), progesterone receptor (PR) and humanepidermal growth factor receptor-۲ (HER-۲) negative MDA-MB-۲۳۱ model fortriple negative breast cancer (TNBC).Methods: Non-fractionated aqueous extract from the inner bark of TA wasused in the experiments. Anchorage dependent growth, anchorage independent(AI) colony formation, cell cycle progression, and expressions of relevantregulatory proteins represented quantitative end points.Results: Long-term treatment for ۲۱ days with the maximum cytostaticconcentration of ۲.۵% TA resulted in a ۹۰% inhibition (P=۰.۰۱۴) in AI colonynumber. Short-term treatment for ۲ days with ۱.۰% TA (IC ) resulted in about a ۱.۳ ۵۰fold increase (P=۰.۰۱۴) in G : S+G /M ratio, about a ۱.۴۸ fold increase (P=۰.۰۱۰) ۱ ۲in the sub G (apoptotic) cells and about a ۳.۲ fold increase (P=۰.۰۱۴) in the pro- ۰apoptotic caspase ۳/۷ activity. Mechanistically, the short-term treatment with ۲.۵%TA decreased Cyclin D۱ expression by about ۸۳.۳%, and pRB expression by about۷۳.۳%.Conclusion: TNBC represents an aggressive cancer notable for its resistance toconventional and targeted therapy. Non-toxic natural substances may representtestable alternatives. This study identifies potential mechanistic leads for TA as anovel naturally occurring testable alternative for secondary prevention/therapy ofTNBC, and validates a novel mechanistic approach to evaluate efficacious nontoxicphytochemicals and herbs as testable alternatives against therapy resistantbreast cancer.

Keywords:

Triple negative breast cancer , Tabebuia avellanedae , cell cycle , RB signaling , cellular apoptosis , caspase ۳/۷ activity