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Xanthohumol activates the proapoptotic arm of the unfolded protein response in chronic lymphocytic leukemia

SOFIE LUST UGent, Barbara Vanhoecke UGent, Mireille Van Gele UGent, Jerina Boelens UGent, Heleen Van Melckebeke UGent, Mary Kaileh, Wim Vanden Berghe UGent, Guy Haegeman UGent, Jan Philippé UGent and Marc Bracke UGent, et al. (2009) ANTICANCER RESEARCH. 29(10). p.3797-3805
abstract
Background: Chronic lymphocytic leukemia (CLL) is an incurable disease with a natural history of increasing resistance to chemotherapy. A novel approach to overcome chemotherapy resistance may be targeting the endoplasmic reticulum (ER). Patients and Methods: The involvement of the unfolded protein response (UPR) in the cell killing effect of xanthohumol (X) was examined in 18 patient. samples. Results: X-induced apoptosis of CLL cells was accompanied by the induction of glucose-regulated protein of 78 kDa (GRP78) and heat-shock protein of 70 kDa (Hsp70) protein levels and by sustained phosphorylation of the eukaryotic translation initiation factor 2 (eIF2a), suggesting the involvement of the ER stress transducer, the double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK). The X-box-binding protein 1 (XBP1) mRNA was spliced but no clear activation of activating transcription factor 6 (ATF6) was observed. The proapoptotic outcome was further demonstrated by the up-regulation of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), down-regulation of myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2), cleavage of poly-(ADP)-ribose polymerase (PARP) and processing of caspase-3, -4 and -9. Furthermore, X showed proteasome inhibitory activity. Conclusion: X stimulates the proapoptotic arm of the UPR in ex vivo CLL cells, suggesting that ER stress may play an important role during X-induced apoptosis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ENDOPLASMIC-RETICULUM STRESS, NF-KAPPA-B, proteasome, apoptosis, XBP1 splicing, ER stress, Chronic lymphocytic leukemia, PROTEASOME INHIBITOR BORTEZOMIB, PANCREATIC-CANCER CELLS, ER STRESS, MULTIPLE-MYELOMA, GENE-EXPRESSION, APOPTOSIS, CLL, P53
journal title
ANTICANCER RESEARCH
Anticancer Res.
volume
29
issue
10
pages
3797 - 3805
Web of Science type
Article
Web of Science id
000271487400009
JCR category
ONCOLOGY
JCR impact factor
1.428 (2009)
JCR rank
125/163 (2009)
JCR quartile
4 (2009)
ISSN
0250-7005
language
English
UGent publication?
yes
classification
A1
id
851426
handle
http://hdl.handle.net/1854/LU-851426
alternative location
http://ar.iiarjournals.org/content/29/10/3797.short
date created
2010-02-04 11:48:42
date last changed
2011-04-18 09:49:20
@article{851426,
  abstract     = {Background: Chronic lymphocytic leukemia (CLL) is an incurable disease with a natural history of increasing resistance to chemotherapy. A novel approach to overcome chemotherapy resistance may be targeting the endoplasmic reticulum (ER). Patients and Methods: The involvement of the unfolded protein response (UPR) in the cell killing effect of xanthohumol (X) was examined in 18 patient. samples. Results: X-induced apoptosis of CLL cells was accompanied by the induction of glucose-regulated protein of 78 kDa (GRP78) and heat-shock protein of 70 kDa (Hsp70) protein levels and by sustained phosphorylation of the eukaryotic translation initiation factor 2 (eIF2a), suggesting the involvement of the ER stress transducer, the double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK). The X-box-binding protein 1 (XBP1) mRNA was spliced but no clear activation of activating transcription factor 6 (ATF6) was observed. The proapoptotic outcome was further demonstrated by the up-regulation of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), down-regulation of myeloid cell leukemia 1 (Mcl-1) and B-cell lymphoma 2 (Bcl-2), cleavage of poly-(ADP)-ribose polymerase (PARP) and processing of caspase-3, -4 and -9. Furthermore, X showed proteasome inhibitory activity. Conclusion: X stimulates the proapoptotic arm of the UPR in ex vivo CLL cells, suggesting that ER stress may play an important role during X-induced apoptosis.},
  author       = {LUST, SOFIE and Vanhoecke, Barbara and Van Gele, Mireille and Boelens, Jerina and Van Melckebeke, Heleen and Kaileh, Mary and Vanden Berghe, Wim and Haegeman, Guy and Philipp{\'e}, Jan and Bracke, Marc and Offner, Fritz},
  issn         = {0250-7005},
  journal      = {ANTICANCER RESEARCH},
  keyword      = {ENDOPLASMIC-RETICULUM STRESS,NF-KAPPA-B,proteasome,apoptosis,XBP1 splicing,ER stress,Chronic lymphocytic leukemia,PROTEASOME INHIBITOR BORTEZOMIB,PANCREATIC-CANCER CELLS,ER STRESS,MULTIPLE-MYELOMA,GENE-EXPRESSION,APOPTOSIS,CLL,P53},
  language     = {eng},
  number       = {10},
  pages        = {3797--3805},
  title        = {Xanthohumol activates the proapoptotic arm of the unfolded protein response in chronic lymphocytic leukemia},
  url          = {http://ar.iiarjournals.org/content/29/10/3797.short},
  volume       = {29},
  year         = {2009},
}

Chicago
LUST, SOFIE, Barbara Vanhoecke, Mireille Van Gele, JERINA BOELENS, Heleen Van Melckebeke, Mary Kaileh, Wim Vanden Berghe, et al. 2009. “Xanthohumol Activates the Proapoptotic Arm of the Unfolded Protein Response in Chronic Lymphocytic Leukemia.” Anticancer Research 29 (10): 3797–3805.
APA
LUST, S., Vanhoecke, B., Van Gele, M., BOELENS, J., Van Melckebeke, H., Kaileh, M., Vanden Berghe, W., et al. (2009). Xanthohumol activates the proapoptotic arm of the unfolded protein response in chronic lymphocytic leukemia. ANTICANCER RESEARCH, 29(10), 3797–3805.
Vancouver
1.
LUST S, Vanhoecke B, Van Gele M, BOELENS J, Van Melckebeke H, Kaileh M, et al. Xanthohumol activates the proapoptotic arm of the unfolded protein response in chronic lymphocytic leukemia. ANTICANCER RESEARCH. 2009;29(10):3797–805.
MLA
LUST, SOFIE, Barbara Vanhoecke, Mireille Van Gele, et al. “Xanthohumol Activates the Proapoptotic Arm of the Unfolded Protein Response in Chronic Lymphocytic Leukemia.” ANTICANCER RESEARCH 29.10 (2009): 3797–3805. Print.