MBD2 inhibitors prevent the protein from binding to methylated DNA, thus turning on suppressed genes.
Researchers at Johns Hopkins Kimmel Cancer Center discovered a small molecule that may prevent prostate cancer cells from using methylation to turn off normal genes.
“One of the proteins in the cell involved in this process is called methyl-CpG binding protein, or MBD,” says lead researcher William Nelson, M.D., Ph.D., professor of oncology and urology.
Previous research in mice missing the MBD2 gene showed that they didn’t develop intestinal polyps. Other studies found that when the gene is removed from cancer cells, suppressed genes are appropriately turned on again.
The John Hopkins team used a two-stage, cell-based, high-throughput screen to find an antagonist for the MBD2 gene, which prevents the protein from binding to methylated genes, and then tested these molecules in cell cultures.
“If the protein can’t bind to the gene, then it can’t keep the gene turned off and the gene is turned back on,” adds Dr. Nelson, “so they may be very exciting lead candidates for the next generation of drugs that may help restore gene function in prostate cancer.”
The findings were presented on October 11 at the Prostate Cancer Foundation’s annual Scientific Retreat.