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. 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
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 MCF-7AROM 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 (E2) target gene expression represented the mechanistic end points. Treatment of MCF-7AROM cells with TNM induced a dose-dependent reduction in E2-promoted anchorage-independent colony number. Mechanistic assays on TNM-treated MCF-7AROM 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 BCL-2 gene expression, and inhibited
aromatase activity. Additionally, TNM treatment downregulated ESR-1 (gene for ER-α),
aromatase and
progesterone gene expression and reduced
mRNA levels of E2 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.