Article

Apoptosis

, Volume 11, Issue 8, pp 1349-1357

Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation

  • Yubin ZhangAffiliated withFirst Department of Internal Medicine, Sapporo Medical University School of MedicineDivision of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University, School of Medicine
  • , Masaaki AdachiAffiliated withFirst Department of Internal Medicine, Sapporo Medical University School of MedicineDivision of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University, School of Medicine Email author 
  • , Rina KawamuraAffiliated withFirst Department of Internal Medicine, Sapporo Medical University School of MedicineDivision of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University, School of Medicine
  • , Hui Chao ZouAffiliated withFirst Department of Internal Medicine, Sapporo Medical University School of MedicineDepartment of Radiology, Sapporo Medical University School of Medicine
  • , Kohzoh ImaiAffiliated withFirst Department of Internal Medicine, Sapporo Medical University School of Medicine
  • , Masato HareyamaAffiliated withDepartment of Radiology, Sapporo Medical University School of Medicine
  • , Yasuhisa ShinomuraAffiliated withFirst Department of Internal Medicine, Sapporo Medical University School of Medicine

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Histone deacetylase (HDAC) inhibitors augment ionizing radiation (IR)-induced apoptosis in several cancer cells by undefined mechanism(s). We recently found that the HDAC inhibitors induce a BH3-only protein Bmf in human squamous carcinoma SAS cells. We extended this study and found that 2.5 nM FK228 pretreatment could not induce apoptosis but augmented IR-induced death. The FK228 pretreatment increased Bmf expression level, and siRNA-mediated knockdown of Bmf transcripts strongly inhibited its augmentation of IR-induced cell death, disruption of mitochondrial membrane potential and DNA fragmentation. Another HDAC inhibitor CBHA pretreatment similarly augmented IR-induced apoptosis, and this effect was also inhibited by Bmf knockdown. Bmf overexpression augmented IR-induced death, and the augmented effects of FK228 were similarly observed in another squamous carcinoma HSC2 cells. Overexpression of histone acetyltransferase p300 mimicked the effects of the HDAC inhibitors, i.e., it enhanced IR-induced death, which was mostly abolished by Bmf knockdown. Taken together, histone hyperacetylation may enhance IR-induced death via activation of Bmf transcription, thereby implying Bmf as a key molecule for HDAC inhibitors (FK228 and CBHA)-mediated enhancing effect on IR-induced cell death.

Keywords

Acetylation Histone deacetylase inhibitor Bmf Apoptosis IR