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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, Mary Kaileh, Wim Vanden Berghe (UGent) , Guy Haegeman (UGent) , Jan Philippé (UGent) , Marc Bracke (UGent) , et al.
(2009) ANTICANCER RESEARCH. 29(10). p.3797-3805
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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.
Keywords
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

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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, Sofie, 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.
@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},
  volume       = {29},
  year         = {2009},
}

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