Dr. Gary’s Nutritional Library

Histone deacetylase inhibitors (HDACis) are a group of chemicals used in the treatment of cancer. They target histone deacetylase enzymes which are important in cancers. These enzymes are proteins which work “epigenetically” since they are able to change the expression of genes without altering the genes. They increase cell differentiation and apoptosis (programmed cell death). HDACis can kill cancer cells which are actively proliferating by inducing apoptosis and by other methods.

A pharmaceutical HDACi, zolinza (vorinostat), has been approved by the Food and Drug Administration (FDA) for treatment of cutaneous T-cell lymphomas. Zolinza has shown success in chronic myelogenous leukemia, acute myeloid leukemia, B cell lymphoma, cancer of breast, prostate, pancreas, colorectum and thyroid as well as non-small-cell lung cancer, Hodgkin lymphoma and non-Hodgkin lymphoma. Butyrate, trichostatin A and valproic acid are HDACis.

Sirtuins are deacetylase enzymes which have different functions and are not altered by the same HDACis. The sirtuins may become important in the therapy of cancer and other diseases. Resveratrol, a sirtuin activator found in red wine, can prevent cancer in mice.

HDACis can be used in combination with other agents. HDACis and retinoic acid work well together for leukemia. (There may be cases in which acetylation is a problem, as in cardiac hypertrophy and failure in mice. Curcumin, a blocker of histone acetyltransferase, is of benefit in this case.)

CONCLUSION: The authors promote the idea that “…increasing acetylation of histones or other proteins through HDAC inhibition is always desirable…” Histone deacetylase inhibitors are being shown to be of benefit in treating cancer. Cancer is starting to emerge as an epigenetic disease.

NOTE: For more information about sirtuins see Summary 206.

Retinoic acid is formed from vitamin A. Retinol is the animal form of retinoic acid.

Trichostatin A is an organic antifungal from Streptomyces.

Read about chlorogenic acid and curcumins as histone deacetylase inhibitors. Curcumin is an extract of turmeric (Curcuma longa).

To read the author’s abstract of the article click on the link to the author’s title of the article above.

PMID: 19008999.

Summary #317.

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