Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines.
(2011) In Experimental Cell Research 317. p.1179-1191- Abstract
- Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line- based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitises DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor, FTI-277, or the... (More)
- Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line- based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitises DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor, FTI-277, or the geranylgeranyl transferase I inhibitor, GGTI-298, indicates that the reduction in cell viability was restricted to inhibition of geranylgeranylation. In addition, treatment with BMS1, a combined inhibitor of farnesyl transferase and Rab GGT, resulted in a high cytostatic effect in WSU-NHL cells, demonstrated by reduced cell viability and decreased proliferation. Co-treatment of BMS1 or GGTI-298 with CHOP showed synergistic effects with regard to markers of apoptosis. We propose that inhibition of protein geranylgeranylation together with conventional cytostatic therapy is a potential novel strategy for treating patients with CHOP refractory DLBCL. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1831790
- author
- Ageberg, Malin LU ; Fjordén, Karin LU ; Lindén, Ola LU ; Linderoth, Johan LU ; Jerkeman, Mats LU and Drott, Kristina LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Experimental Cell Research
- volume
- 317
- pages
- 1179 - 1191
- publisher
- Academic Press
- external identifiers
-
- wos:000289336700009
- pmid:21324313
- scopus:79953100959
- ISSN
- 1090-2422
- DOI
- 10.1016/j.yexcr.2011.02.006
- language
- English
- LU publication?
- yes
- id
- 2bad8a01-640a-4cfa-ad5a-8c70cd7ef201 (old id 1831790)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21324313?dopt=Abstract
- date added to LUP
- 2016-04-04 07:38:05
- date last changed
- 2022-01-29 02:22:05
@article{2bad8a01-640a-4cfa-ad5a-8c70cd7ef201, abstract = {{Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line- based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitises DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor, FTI-277, or the geranylgeranyl transferase I inhibitor, GGTI-298, indicates that the reduction in cell viability was restricted to inhibition of geranylgeranylation. In addition, treatment with BMS1, a combined inhibitor of farnesyl transferase and Rab GGT, resulted in a high cytostatic effect in WSU-NHL cells, demonstrated by reduced cell viability and decreased proliferation. Co-treatment of BMS1 or GGTI-298 with CHOP showed synergistic effects with regard to markers of apoptosis. We propose that inhibition of protein geranylgeranylation together with conventional cytostatic therapy is a potential novel strategy for treating patients with CHOP refractory DLBCL.}}, author = {{Ageberg, Malin and Fjordén, Karin and Lindén, Ola and Linderoth, Johan and Jerkeman, Mats and Drott, Kristina}}, issn = {{1090-2422}}, language = {{eng}}, pages = {{1179--1191}}, publisher = {{Academic Press}}, series = {{Experimental Cell Research}}, title = {{Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines.}}, url = {{http://dx.doi.org/10.1016/j.yexcr.2011.02.006}}, doi = {{10.1016/j.yexcr.2011.02.006}}, volume = {{317}}, year = {{2011}}, }