Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET

Patrick Brest, Mattias Gustafsson, Ann Kristin Mossberg, Lotta Gustafsson, Caroline Duringer, Ali Hamiche, Catharina Svanborg

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Histone deacetylase inhibitors (HDIs) and HAMLET (human α-lactalbumin made lethal to tumor cells) interact with histones, modify the structure of chromatin, and trigger tumor cell death. This study investigated how the combination of HDIs and HAMLET influences cell viability, histone acetylation, and DNA integrity. The pretreatment of tumor cells with HDIs was shown to enhance the lethal effect of HAMLET and the histone hyperacetylation response to HDIs increased even further after HAMLET treatment. HDIs and HAMLET were shown to target different histone domains as HAMLET bound tailless core histones, whereas HDIs modify the acetylation of the histone tail. DNA damage in response to HAMLET was increased by HDIs. The DNA repair response (p21WAFI expression) was induced by both agonists but abolished when the two agonists were combined. The results suggest that the synergy of HDIs and HAMLET is based on different but converging death pathways, both involving chromatin alterations. We speculate that HAMLET and HDIs might be combined to promote tumor cell death in vivo.

Original languageEnglish
Pages (from-to)11327-11334
Number of pages8
JournalCancer Research
Volume67
Issue number23
DOIs
Publication statusPublished - 1 Dec 2007
Externally publishedYes

Fingerprint

Histone Deacetylase Inhibitors
Histones
Acetylation
Chromatin
Neoplasms
Cell Death
Lactalbumin
DNA Repair
DNA Damage
Tail
Cell Survival
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Brest, P., Gustafsson, M., Mossberg, A. K., Gustafsson, L., Duringer, C., Hamiche, A., & Svanborg, C. (2007). Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. Cancer Research, 67(23), 11327-11334. https://doi.org/10.1158/0008-5472.CAN-07-1153

Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. / Brest, Patrick; Gustafsson, Mattias; Mossberg, Ann Kristin; Gustafsson, Lotta; Duringer, Caroline; Hamiche, Ali; Svanborg, Catharina.

In: Cancer Research, Vol. 67, No. 23, 01.12.2007, p. 11327-11334.

Research output: Contribution to journalArticle

Brest, P, Gustafsson, M, Mossberg, AK, Gustafsson, L, Duringer, C, Hamiche, A & Svanborg, C 2007, 'Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET', Cancer Research, vol. 67, no. 23, pp. 11327-11334. https://doi.org/10.1158/0008-5472.CAN-07-1153
Brest P, Gustafsson M, Mossberg AK, Gustafsson L, Duringer C, Hamiche A et al. Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. Cancer Research. 2007 Dec 1;67(23):11327-11334. https://doi.org/10.1158/0008-5472.CAN-07-1153
Brest, Patrick ; Gustafsson, Mattias ; Mossberg, Ann Kristin ; Gustafsson, Lotta ; Duringer, Caroline ; Hamiche, Ali ; Svanborg, Catharina. / Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET. In: Cancer Research. 2007 ; Vol. 67, No. 23. pp. 11327-11334.
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