Anti-proliferative Activities of Solvent Fractions of Lees Extracts in Human Colorectal HCT116 Cells

In the present study, we prepared eighty-five different kinds of lees extracts and their solvent fractions and investigated their anti-proliferative activities against human colorectal cancer HCT116 cells. HCT116 cells were treated with eighty-five solvent fractions of lees extracts and then cell viability was measured using MTS assay. Among the treated solvent fractions, three solvent fractions (KSD-E1-3, KSD-E2-3, and KSD-E4-3) were selected based on cell viability assay. In addition, we performed an oligo DNA microarray analysis to analyze the gene expression changes by treatment of KSD-E1-3 in HCT116 cells. Among the upregulated genes, we selected 4 genes (NAG-1, ATF3, p21, and DDIT3) and performed RT-PCR using gene-specific primers. Among the treated solvent fractions, KSD-E1-3 dramatically induced the expressions of the four selected genes. In addition, we investigated whether the upregulations of those genes were dependent on the transcription factor p53`s presence using p53 null HCT116 cells. The results indicate that the upregulations of NAG-1, ATF3, and DDIT3 are not dependent on the p53 presence, whereas p21 is dependent on the p53 presence. These findings may help to understand the molecular mechanisms of the anti-proliferative activity mediated by rice wine lees in human colorectal cancer cells.