Selective
estrogen receptor (ER) modulators are used as a
therapy for ER+ clinical
breast cancer, but they exhibit adverse effects.
Herbal medicines may provide an alternative or complementary approach.
Taheebo, extracted from the inner bark of the Tabebuia avellandae tree found in the Brazilian Amazon, exhibits selective anti-proliferative effects in
carcinoma cell lines. The present study identifies the mechanistic leads for the inhibitory effects of
Taheebo. Human
breast carcinoma derived ER+MCF-7 cells were used as the model. Aqueous extract of
Taheebo was the test compound. Cell cycle analysis, clonogenic assay, and global gene expression profiles were the quantitative parameters.
Taheebo treatment resulted in a dose/time-dependent growth inhibition (S phase arrest, reduced clonogeneticity) and initiation of apoptosis (
chromatin condensation). A 6-h treatment with 1.5 mg/ml
Taheebo modulated the gene expression of G2 specific
cyclin B1 (-2.0-fold); S phase specific
PCNA (-2.0-fold) and OKL38 (+11.0-fold); apoptosis specific GADD-45 family (+1.9-5.4-fold),
Caspases (+1.6-1.7-fold), BCL-2 family (-1.5-2.5-fold),
estrogen responsive ESR1 (-1.5-fold), and xeno-biotic metabolism specific
CYP 1A1 (+19.8 fold) and CYP 1B1 (+7.9-fold). The anti-proliferative effects of
Taheebo correlate with down-regulated cell cycle regulatory and
estrogen responsive genes, and up-regulated apoptosis specific and xeno-biotic metabolism specific genes. These data validate a rapid mechanistic approach to prioritize efficacious
herbal medicines, thereby complementing the existing endocrine
therapy for
breast cancer.