DNA microarray analysis of gene expression changes in ICR mouse liver following treatment with active hexose correlated compound

Abstract

Active hexose correlated compound (AHCC) is a mixture of glucan-rich polysaccharides isolated from the culture extract of shiitake mushroom mycelium. Multiple bioactivities, including immune regulation, have been reported in both basic and clinical studies. This compound has also been used as an adjunct treatment for cancer, but no study has examined whether AHCC can alter the metabolism of therapeutic agents, such as anticancer drugs, in the liver by altering the expression of drug-metabolizing enzymes. Here, we assessed AHCC-induced changes in the expression of genes encoding drug-metabolizing enzymes using a DNA microarray.A 3% AHCC solution was provided ad libitum for 5 days to ICR mice, followed by liver excision, total RNA extraction, and DNA microarray analyses using the Genopal® Metabolic chip (195 genes) and Oxidative stress chip (219 genes). The Metabolic chip identified eight differentially expressed genes (DEGs), defined by a minimum 2.0-fold change in expression from that in control mice. Of these DEGs, two involved in drug metabolism exhibited modest upregulation (CYP3A11, signal intensity ratio [SIR] = 1.15 and CYP7A1, SIR = 1.02). In addition, the Oxidative stress chip identified 23 DEGs, of which five (BCL10, BCL6, ICAM1, MAP3K5, and CASP9) showed very strong suppression (SIR < -10).Oral administration of AHCC to healthy mice altered the expression of multiple genes in the liver, including slight upregulation of drug-metabolizing enzymes and marked suppression of genes involved in tumor necrosis factor signaling and apoptosis. Thus, AHCC may protect liver function against the adverse effects of anticancer agents, such as inflammation, while having little effect on drug metabolism.