Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70.

Abstract

Histone deacetylases (HDACs) are a group of enzymes that regulate gene transcription by controlling deacetylation of histones and non-histone proteins. Overexpression of HDACs is found in some types of tumors and predicts poor prognosis. Five HDAC inhibitors are approved for the treatment of cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and multiple myeloma. Treatment with HDAC inhibitors regulates gene expression with increased acetylated histones with unconfirmed connection with therapy. Apoptosis is a key mechanism by which HDAC inhibitors selectively kill cancer cells, probably due to acetylation of non-histone proteins. Ku70 is a protein that repairs DNA breaks and stabilizes anti-apoptotic protein c-FLIP and proapoptotic protein Bax, which is regulated by acetylation. HDAC inhibitors induce Ku70 acetylation with repressed c-FLIP and activated Bax in cancer cells. Current studies indicate that Ku70 is a potential target of HDAC inhibitors and plays an important role during the induction of apoptosis.

• Authors: Ping Gong, Yuetong Wang, Yongkui Jing
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 7 (Mar 30 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30935057 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Ku Autoantigen

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis
• Histone Deacetylase Inhibitors (pharmacology, therapeutic use)
• Humans
• Ku Autoantigen (genetics, metabolism)
• Neoplasms (drug therapy, metabolism)