Genistein increases gene expression by demethylation of WNT5a promoter in colon cancer cell line SW1116.

Genistein (GEN), one of the soy isoflavones, exhibits protection against colon cancer. The WNT signaling pathway plays a critical role in both normal epithelial regeneration and tumorigenesis in human colon. In this study it was hypothesized that GEN regulates specific genes in the WNT signaling pathway. Colon cancer cell lines DLD-1, SW480, and SW1116 were treated with Novasoy or GEN for 4 days. mRNA levels of several WNT signaling components were analyzed by real-time PCR. Methylation-specific PCR and bisulfite genomic sequencing were used to analyze the methylation status of CpG islands. Both Novasoy and GEN inhibited cell proliferation in all three cell lines. WNT5a mRNA showed a time-dependent induction by Novasoy and GEN in DLD-1 cells but only by GEN in SW1116 cells. Meanwhile, WNT5a CpG island methylation level was decreased in SW1116 by GEN. In conclusion, GEN regulated WNT5a expression, which was accompanied by a decrease in DNA methylation level at the analyzed CpG island.