The use of histone deacetylase inhibitors for the treatment of endometriosis

Altering epigenetics: A new avenue for the treatment of endometriosis?

Key Points

Highlights:

• Histone deacetylase inhibitors show promise for the treatment of endometriosis.

Key Results:

• Trichostatin A, a histone deacetylase inhibitor, has been shown to induce expression of NAG-1 and increase the apoptosis of endometriotic stromal cells.
• Valproic acid has also been seen to induce apoptosis of endometriotic stromal cells and decrease endometriotic implant size in mice but has not been studied in clinical trials on humans.
• Histone deacetylase inhibitors seem to be a promising avenue for the development of drugs against endometriosis. However, their safety profiles and feasibility still require investigation.

What’s done here?

• This article is a short letter in response to one study that investigated the use of trichostatin A, a histone deacetylase inhibitor, to induce NAG-1 expression and subsequently reduce endometriotic stromal cell growth and progression.

Limitations:

• This article is purely a response to a preliminary study on the use of Trichostatin A on endometriosis apoptosis.

Lay Summary

Histone deacetylase inhibitors prevent the deacetylation of specific gene sequences thereby allowing the increased transcription of certain genes. Trichostatin A, a histone deacetylase inhibitor, has been seen to induce the expression of a pro-apoptotic gene called nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1). Increased expression of this gene has been observed to increase the apoptosis of endometriotic stromal cells in an investigation by Seo and colleagues. They concluded that epigenetic aberrations that decrease the expression of these pro-apoptotic genes could be involved in the pathogenesis and survival of endometriotic cells. In animal studies, the use of these inhibitors has demonstrated to inhibit the proliferation and decrease the number and size of endometriotic implants.

The authors of the article note that Trichostatin A is a drug that still requires investigation, as the preclinical data on its pharmacokinetics and safety profile have yet to be fully elucidated. Valproic acid, a drug widely used to treat epilepsy, has also been seen to induce apoptosis of endometriotic stromal cells and is known to be safe. Valproic acid has this effect by inhibiting the P450 aromatase, thereby decreasing the estrogen production of implanted endometriotic cells. It also induces p21, a proapoptotic protein. Valproic acid has been used in patients with adenomyosis in a small study but could also be a potential treatment option for women with endometriosis. However, clinical studies investigating its use in endometriosis are needed.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29575999