Inhibitory effect of AHCC and GCP on tumorigenesis of C6 glioma cells in culture medium and rats mediated by downregulating CD133 and Nestin expressions (842.13)

Abstract

The CD133 and Nestin proteins are described as cancer stem cell markers. Norepinephrine (NE) is a sympathetic neurotransmitter, studies have indicated the level of NE or the active degree of adrenoceptors in certain bodily tissues correlates with the degree of tumorigenesis in those tissues. To explore the relation between the activation of adrenoceptors and the expression level of CD133 and Nestin proteins, we investigated whether NE might regulate the expression of CD133 and Nestin and its signaling pathway; the effect of AHCC (Active Hexose Correlated Compound) &and GCP (Genistein Concentrated Polysaccharide) on the expression of CD133 and Nestin and the sphere‐colony formation of C6 cells in medium and the tumorigenesis in rats inoculated subcutaneously with C6 cells.We measured the expression level of CD133 and Nestin in C6 cells with western blot analysis, examined the sphere‐colony formation of the cells by sphere assay and measured the tumor volume in rats calculated as length × width × depth × 0.5236.We found out the expressions of CD133 and Nestin in C6 cells were significantly upregulated by NE stimulation. Further analysis showed prazosin completely blocked the NE‐induced upregulation of CD133 and Nestin expressions, while propranolol had no influence to them. Pretreatment with LY294002, blocked the NE‐induced upregulation of CD133 expression, but showed no influence to Nestin expression. Pretreatment with B3806, blocked the NE‐induced upregulation of Nestin expression, but had no significant influence to CD133 expression in the cells. Co‐culture with AHCC or GCP, the upregulated effects on the expressions of CD133 and Nestin induced by NE in the cells were weaken and the sphere size of the cells became smaller. The animal experiment in rats showed that the tumor size was markedly smaller in AHCC or GCP group than in control group.Based on these findings, we thus assume that AHCC & GCP can ameliorate some kinds of tumorigenesis in cancer stem cells expressing CD133 and Nestin proteins.