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Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET.

Brest, Patrick LU ; Gustafsson, Mattias LU ; Mossberg, Anki LU ; Gustafsson, Lotta LU orcid ; Düringer, Caroline LU ; Hamiche, Ali and Svanborg, Catharina LU (2007) In Cancer Research 67(23). p.11327-11334
Abstract
Histone deacetylase inhibitors (HDIs) and HAMLET (human alpha-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... (More)
Histone deacetylase inhibitors (HDIs) and HAMLET (human alpha-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. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
Histone Deacetylases: metabolism, Histones: metabolism, Histone Deacetylases: antagonists & inhibitors, Hela Cells: drug effects, Enzyme Inhibitors: pharmacology, Cyclin-Dependent Kinase Inhibitor p21: metabolism, Chromatin: ultrastructure, Chromatin: metabolism, Chromatin: drug effects, Cell Survival: drug effects, Acetylation: drug effects, Oleic Acids: pharmacology, Lactalbumin: pharmacology, Jurkat Cells: drug effects, Hydroxamic Acids: pharmacology
in
Cancer Research
volume
67
issue
23
pages
11327 - 11334
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:18056459
  • scopus:37049000403
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-07-1153
project
HAMLET- In vivo effects and mechanisms of tumor cells death
language
English
LU publication?
yes
id
4b84a088-63ec-4f94-b0cb-48f6415aee52 (old id 1035674)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18056459?dopt=Abstract
date added to LUP
2016-04-04 09:03:30
date last changed
2024-01-12 08:27:42
@article{4b84a088-63ec-4f94-b0cb-48f6415aee52,
  abstract     = {{Histone deacetylase inhibitors (HDIs) and HAMLET (human alpha-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.}},
  author       = {{Brest, Patrick and Gustafsson, Mattias and Mossberg, Anki and Gustafsson, Lotta and Düringer, Caroline and Hamiche, Ali and Svanborg, Catharina}},
  issn         = {{1538-7445}},
  keywords     = {{Histone Deacetylases: metabolism; Histones: metabolism; Histone Deacetylases: antagonists & inhibitors; Hela Cells: drug effects; Enzyme Inhibitors: pharmacology; Cyclin-Dependent Kinase Inhibitor p21: metabolism; Chromatin: ultrastructure; Chromatin: metabolism; Chromatin: drug effects; Cell Survival: drug effects; Acetylation: drug effects; Oleic Acids: pharmacology; Lactalbumin: pharmacology; Jurkat Cells: drug effects; Hydroxamic Acids: pharmacology}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{11327--11334}},
  publisher    = {{American Association for Cancer Research Inc.}},
  series       = {{Cancer Research}},
  title        = {{Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET.}},
  url          = {{http://dx.doi.org/10.1158/0008-5472.CAN-07-1153}},
  doi          = {{10.1158/0008-5472.CAN-07-1153}},
  volume       = {{67}},
  year         = {{2007}},
}