Genome-wide transcriptome analysis reveals inactivation of Wnt/β-catenin by 3,3'-diindolylmethane inhibiting proliferation of colon cancer cells.

Abstract

Multiple genetic and signaling pathway alterations underlie the development of colon cancer. We utilized genome-wide transcriptome analysis to identify important gene expression patterns following treatment with 3,3'-diindolylmethane (DIM), a natural compound derived from cruciferous vegetables, on colon cancer cells. Statistical analyses of gene expression data from DIM treated cells revealed that 692genes were significantly upregulated, while 731genes were down-regulated. Putative gene networks showed that several oncogenes (β-catenin, Myc and FOS) were significantly suppressed by DIM treatment. Using clinical data from colon cancer patients, activation of β-catenin was found to be significantly associated with patient prognosis by Kaplan-Meir plot analysis. We validated the mRNA and protein expression levels of c-Myc, β-catenin, and cyclin D1, all of which were significantly suppressed after DIM treatment in DLD-1 and HCT116 cells. System level characterization of our findings suggests for the first time that β-catenin and c-Myc, which are major genes involved in colon carcinogenesis, were significantly downregulated by DIM treatment in colon cancer cells. Therefore, targeting Wnt/β-catenin signaling by DIM may be an attractive strategy for the prevention and treatment of colon cancer.