The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3733949
- author
- Ageberg, Malin LU ; Fjordén, Karin LU ; Relander, Thomas LU and Drott, Kristina LU
- organization
- publishing date
- 2013
- 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}}, }