HDAC inhibition and Cancerdialysis
Author: Sture Hobro
Inhibition of HDACs to reverse epigenetic alterations in cancer has been shown to induce powerful anticancer properties. The combination of HDAC inhibitors with standard chemotherapeutic drugs has demonstrated promising anticancer effects in clinical studies. Today, several HDAC inhibitors (of one or more of HDAC1, 2, 3 and 6) are approved for some cancers and many ongoing clinical trials for additional drugs are ongoing.
Histone deacetylases (HDACs) are proteins that help regulate gene expression. They do this by removing a molecule called an acetyl group from other proteins in the cell. HDACs have been shown to play a role in cancer by promoting the growth and survival of cancer cells. Beside numerous other cancers promoting effects they do this by blocking a process called apoptosis, which is a natural way for the body to get rid of damaged or abnormal cells as cancer. Another equally important effect from HDACs is their ability to help cancer cells to resist treatment by repairing DNA damage caused by chemotherapy or radiation therapy. But just two examples of many on how increased HDACs helps cancer to survive treatments
Figure: Beta-hydroxybutyrate is a physiological inhibitor of not less than eight different HDACs and is not likely to induce significant side effects. The ketone Beta-hydroxybutyrate (BHB) is a molecule that is produced by the liver during CancerDialysis. BHB has been shown to have anti-cancer properties by inhibiting the growth of cancer cells. One way it does this is by inhibiting the activity of many HDACs (1-9 except 6). By inhibiting HDACs, BHB increases the acetylation of histones, which are proteins that help package DNA in cells. This leads to changes in gene expression that reduces cancer cells protect against oxidative stress, immune system and increase cancer cells willingness for self-destruction (apoptosis).
