Growth inhibitory efficacy and anti-aromatase activity of in a model for post-menopausal Luminal A breast cancer.

Aromatase inhibitors (AIs) represent a treatment option for post-menopausal estrogen receptor-positive (ER) 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. (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 growth 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 MCF-7 cells stably transfected with the aromatase gene 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) target gene expression represented the mechanistic end points. Treatment of MCF-7 cells with TNM induced a dose-dependent reduction in E-promoted anchorage-independent colony number. Mechanistic assays on TNM-treated MCF-7 cells demonstrated that TNM at a concentration of 10 µg (NFD content: 2 ng), induced S-phase arrest, increased pro-apoptotic caspase 3/7 activity, increased pro-apoptotic BAX and decreased anti-apoptotic gene expression, and inhibited aromatase activity. Additionally, TNM treatment downregulated (gene for ER-α), aromatase and progesterone gene expression and reduced mRNA levels of E target genes , and . 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.