Abstract
Breast cancer is the most common cancer among women in the United States, and worldwide over one million new cases are diagnosed each year. Preliminary studies by Panee and colleagues demonstrated that 0.5% (w/w) dietary supplementation with an ethanol/water extract from bamboo Phyllostachys edulis inhibited the incidence of 7,12‐dimethylbenz[a]anthracene (DMBA, a carcinogen)‐induced mammary tumors in female Sprague‐Dawley rats by 44% and dramatically reduced tumor multiplicity. This project has aimed to delineate the anti‐breast cancer mechanisms of this bamboo extract (BEX) in the aforementioned rat model. We hypothesized that BEX may alter the gene expression of key proteins involved in estrogen‐ and/or growth factor‐signaling pathways and xenobiotic biotransforming enzymes in the mammary tumors. To test this hypothesis, we extracted RNA from individual mammary tumors that were harvested from each rat. Then, we synthesized complementary DNA (cDNA) and combined the cDNA samples according to each rat's dietary group— BEX‐supplemented rat diet or control rat diet. Using quantitative real‐time polymerase chain reaction, we measured expression levels of target genes that included the following: estrogen receptors alpha and beta (ER‐α and ‐β), human epidermal growth factor receptor 2 (HER2), and all glutathioine‐s‐transferase (GST) isoforms. Comparison between study groups revealed that BEX‐supplementation significantly downregulated the gene expression of ER‐α, ER‐β, and HER2 in the mammary tumors by 65%, 70%, and 67% respectively (p < 0.0001). Additionally, the mammary tumors expressed all GST isoforms, whereby GSTa4 and GSTp1 resulted in high abundant values. Interestingly, BEX supplementation also significantly downregulated the gene expression of GSTa4 and GSTp1 by 32% and 31% respectively (p < 0.005). Our observations have indicated that the downregulation of ER‐α, ER‐β, and HER2 gene expression in the mammary tumors may contribute to the anti‐breast cancer effect of BEX, and that BEX may also reduce chemoresistance in the mammary tumors by inhibiting the gene expression of xenobiotic biotransforming enzyme GST.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B155.