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The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death.

Ageberg, Malin LU ; Fjordén, Karin LU ; Relander, Thomas LU and Drott, Kristina LU (2013) In American Journal of Translational Research 5(2). p.170-183
Abstract
Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematological malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60% of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC... (More)
Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematological malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60% of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC inhibitor valproic acid (VPA) on DLBCL cell lines. To elucidate the effects of VPA on chemo-sensitivity, we used a cell-line based model of CHOP-refractory DLBCL. All five DLBCL cell lines treated with VPA alone or in combination with CHOP showed decreased viability and proliferation. The VPA-induced sensitization of DLBCL cells to cytotoxic treatment resulted in increased number of apoptotic cell as judged by annexin V-positivity and the presence of cleaved caspase-3. In addition, pretreatment with VPA resulted in a significantly increased DNA-damage as compared to CHOP alone. In summary, HDAC inhibitors such as VPA, are promising therapeutic agents in combination with R-CHOP for patients with DLBCL. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Translational Research
volume
5
issue
2
pages
170 - 183
publisher
e-Century Publishing
external identifiers
  • wos:000318281300006
  • pmid:23573362
  • scopus:84875794890
ISSN
1943-8141
language
English
LU publication?
yes
id
4ae71d03-69fa-4682-82d9-e4284f776a2c (old id 3733949)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23573362?dopt=Abstract
date added to LUP
2016-04-01 13:08:29
date last changed
2022-01-27 17:34:15
@article{4ae71d03-69fa-4682-82d9-e4284f776a2c,
  abstract     = {{Epigenetic code modifications by histone deacetylase inhibitors (HDACis) have recently been proposed as potential new therapies for hematological malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive lymphoma. At present, standard first line treatment for DLBCL patients is the antracycline-based chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) combined with the monoclonal anti-CD20 antibody rituximab (R-CHOP). Since only 50-60% of patients reach a long-time cure by this treatment, there is an urgent need for novel treatment strategies to increase the response and long-term remission to initial R-CHOP therapy. In this study, we investigated the effect of the HDAC inhibitor valproic acid (VPA) on DLBCL cell lines. To elucidate the effects of VPA on chemo-sensitivity, we used a cell-line based model of CHOP-refractory DLBCL. All five DLBCL cell lines treated with VPA alone or in combination with CHOP showed decreased viability and proliferation. The VPA-induced sensitization of DLBCL cells to cytotoxic treatment resulted in increased number of apoptotic cell as judged by annexin V-positivity and the presence of cleaved caspase-3. In addition, pretreatment with VPA resulted in a significantly increased DNA-damage as compared to CHOP alone. In summary, HDAC inhibitors such as VPA, are promising therapeutic agents in combination with R-CHOP for patients with DLBCL.}},
  author       = {{Ageberg, Malin and Fjordén, Karin and Relander, Thomas and Drott, Kristina}},
  issn         = {{1943-8141}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{170--183}},
  publisher    = {{e-Century Publishing}},
  series       = {{American Journal of Translational Research}},
  title        = {{The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death.}},
  url          = {{https://lup.lub.lu.se/search/files/3182602/4017272.pdf}},
  volume       = {{5}},
  year         = {{2013}},
}