Growth inhibitory efficacy and anti‑aromatase activity of Tabebuia avellanedae in a model for post‑menopausal Luminal A breast cancer

Aromatase inhibitors (AIs) represent a treatment option for post-menopausal estrogen receptor-positive ([ER.sup.+]) breast cancer as monotherapy, or in combination with cyclin-dependent kinase 4/6 or mTOR inhibitors. Long-term treatment with these agents leads to dose-limiting toxicity and drug resistance. Natural substances provide testable alternatives to current therapy. Tabebuia avellanedae (TA) tree is indigenous to the Amazon rainforest. The inner bark of TA represents a medicinal dietary supplement known as Taheebo. Non-fractionated aqueous extract from TA is an effective grow th inhibitor in the Luminal A and triple negative breast cancer models. The quinone derivative naphthofurandione (NFD) is a major bioactive agent in TA. The present study examined the efficacy of finely ground powder from the inner bark of TA, available under the name of Taheebo-NFD-Marugoto (TNM). The [ER.sup.+] MCF-7 cells stably transfected with the aromatase gene [MCF-7.sup.AROM] represented a model for aromatase-expressing post-menopausal breast cancer. Anchorage-independent colony formation, cell cycle progression, pro-apoptotic caspase 3/7 activity, apoptosis-specific gene expression, aromatase activity and select estradiol ([E.sub.2]) target gene expression represented the mechanistic end points. Treatment of [MCF-7.sup.AROM] cells with TNM induced a dose-dependent reduction in [E.sub.2]-promoted anchorage-independent colony number. Mechanistic assays on TNM-treated [MCF-7.sup.AROM] cells demonstrated that TNM at a concentration of 10 [micro]g (NFD content: 2 ng), induced S-phase arrest, increased pro-apoptotic caspase 3/7 activity, increased pro-apoptotic BAX and decreased anti-apoptotic BCL-2 gene expression, and inhibited aromatase activity. Additionally, TNM treatment downregulated ESR-1 (gene for ER-[alpha]), aromatase and progesterone gene expression and reduced mRNA levels of [E.sub.2] target genes pS2, GRB2 and cyclin D1. Inhibition of aromatase activity, based on the NFD content of TNM was superior to the clinical AIs Letrozole and Exemestane. These data demonstrated the potential efficacy of TNM as a nutritional alternative for current therapy of aromatase positive, post-menopausal breast cancer. Key words: Tabebuia avelanedae, growth inhibition, aromatase inhibition, breast cancer cells