Mechanistic Studies on the Inhibitory Effect of Bamboo Extract on the Proliferation of Breast Cancer Cell Lines

Abstract

Previous research conducted in our laboratory has shown that an extract from bamboo, Phyllostachys edulis, inhibited the development of mammary tumors in female Sprague-Dawley rats treated with 7,12-dimethylbenz[a]anthracene. In addition, the presence of this bamboo extract (BEX) in the cell culture media dramatically inhibited the proliferation of estrogen receptor (ER) positive human breast cancer cell lines T47D and MCF7, but had no inhibitory effect on the ER negative breast cancer cell line MDA-MB-231 and on ER negative non-carcinoma mammary epithelial MCF10A cells. This project employed in vitro cell culture models to investigate the molecular mechanism of the anti-breast cancer function of BEX. T47D, MCF7, MDA-MB-231 and MCF10A cells were incubated with 0.5% (v/v) BEX or the same volume of ethanol as a solvent control for 3 or 7 days, and the total antioxidant capacity of the cells, the cellular contents of total glutathione (GSH, the most abundant thiol antioxidant in mammalian cells), and the mRNA levels of γ-glutamylcysteine synthetase heavy chain and light chain (GCS-HC and GCS-LC, the two subunits of a rate-limiting enzyme in glutathione biosynthesis) were measured. Further studies focusing on T47D cells measured the gene expression and enzymatic activity of galactosidase β1 (GLB1, a biomarker of cellular senescence) as well as the gene expression of estrogen receptor alpha (ERα, involved in breast cancer development and metastasis). Our results showed that the highest increases of total antioxidant capacity and total intracellular GSH were found in MCF7 and T47D cells, and under most conditions, the presence of BEX in the cell culture media increased the gene expression of GCS-HC and GCS-LC. BEX treatment also increased the gene expression and enzymatic activity of GLB1, and decreased the gene expression of ERα in T47D cells. The results indicate that BEX may exert the anti-breast cancer function through multiple and potentially synergistic pathways, including improving antioxidant status in breast cancer cells, regulating cellular senescence, and inhibiting the gene expression of ERα. The biomarkers highlighted in this project will be used for active compound fractionation and identification in future studies. Abbreviations: BEX, Bamboo extract; EtOH, ethanol; DMBA, 7,12-dimethylbenz[a]anthracene; GCS-HC, γ-glutamylcysteine synthetase heavy chain; GCS-LC, γ-glutamylcysteine synthetase light chain; GSH, glutathione; ERα , estrogen receptor alpha; ERβ, estrogen receptor beta; GLBl, galactosidase beta 1.