Growth inhibition of estrogen receptor positive human breast cancer cells by Taheebo from the inner bark of Tabebuia avellandae tree.
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.
Mukherjee
B
B
Strang Cancer Prevention Center, New York, NY, USA.
Telang
N
N
Wong
G Y C
GY
D017209:Apoptosis / Q000187:drug effects; D001938:Brazil; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019926:Cyclin B / Q000235:genetics; D056744:Cyclin B1; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029663:Tabebuia / Q000737:chemistry*; D013997:Time Factors
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D010936:Plant Extracts; D028321:Plant Preparations; D011960:Receptors, Estrogen; C543691:Taheebo; D019363:Cytochrome P-450 CYP1A1