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The TRAIL apoptotic pathway mediates proteasome inhibitor induced apoptosis in primary chronic lymphocytic leukemia cells.
Apoptosis. 2006 Jul; 11(7):1175-93.A

Abstract

The proteasome inhibitors are a new class of antitumor agents. These inhibitors cause the accumulation of many proteins in the cell with the induction of apoptosis including TRAIL death receptors DR4 and DR5, but the role of the TRAIL apoptotic pathway in proteasome inhibitor cytotoxicity is unknown. Herein, we have demonstrated that the induction of apoptosis by the proteasome inhibitors, MG-132 and PS-341 (bortezomib, Velcade), in primary CLL cells and the Burkitt lymphoma cell line, BJAB, is associated with up-regulation of TRAIL and its death receptors, DR4 and DR5. In addition, FLICE-like inhibitory protein (c-FLIP) protein is decreased. MG-132 treatment increases binding of DR5 to the adaptor protein FADD, and causes caspase-8 activation and cleavage of pro-apoptotic BID. Moreover, DR4:Fc or blockage of DR4 and DR5 expression using RNA interference, which prevents TRAIL apoptotic signaling, blocks proteasome inhibitor induced apoptosis. MG-132 also increases apoptosis and DR5 expression in normal B-cells. However, when the proteasome inhibitors are combined with TRAIL or TRAIL receptor activating antibodies the amount of apoptosis is increased in CLL cells but not in normal B cells. Thus, activation of the TRAIL apoptotic pathway contributes to proteasome inhibitor induced apoptosis in CLL cells.

Authors+Show Affiliations

Manitoba Institute of Cell Biology, Cancer Care Manitoba, University of Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16699949

Citation

Kabore, Albert F., et al. "The TRAIL Apoptotic Pathway Mediates Proteasome Inhibitor Induced Apoptosis in Primary Chronic Lymphocytic Leukemia Cells." Apoptosis : an International Journal On Programmed Cell Death, vol. 11, no. 7, 2006, pp. 1175-93.
Kabore AF, Sun J, Hu X, et al. The TRAIL apoptotic pathway mediates proteasome inhibitor induced apoptosis in primary chronic lymphocytic leukemia cells. Apoptosis. 2006;11(7):1175-93.
Kabore, A. F., Sun, J., Hu, X., McCrea, K., Johnston, J. B., & Gibson, S. B. (2006). The TRAIL apoptotic pathway mediates proteasome inhibitor induced apoptosis in primary chronic lymphocytic leukemia cells. Apoptosis : an International Journal On Programmed Cell Death, 11(7), 1175-93.
Kabore AF, et al. The TRAIL Apoptotic Pathway Mediates Proteasome Inhibitor Induced Apoptosis in Primary Chronic Lymphocytic Leukemia Cells. Apoptosis. 2006;11(7):1175-93. PubMed PMID: 16699949.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The TRAIL apoptotic pathway mediates proteasome inhibitor induced apoptosis in primary chronic lymphocytic leukemia cells. AU - Kabore,Albert F, AU - Sun,Jinmie, AU - Hu,Xiaojie, AU - McCrea,Kristin, AU - Johnston,James B, AU - Gibson,Spencer B, PY - 2006/5/16/pubmed PY - 2006/9/12/medline PY - 2006/5/16/entrez SP - 1175 EP - 93 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 11 IS - 7 N2 - The proteasome inhibitors are a new class of antitumor agents. These inhibitors cause the accumulation of many proteins in the cell with the induction of apoptosis including TRAIL death receptors DR4 and DR5, but the role of the TRAIL apoptotic pathway in proteasome inhibitor cytotoxicity is unknown. Herein, we have demonstrated that the induction of apoptosis by the proteasome inhibitors, MG-132 and PS-341 (bortezomib, Velcade), in primary CLL cells and the Burkitt lymphoma cell line, BJAB, is associated with up-regulation of TRAIL and its death receptors, DR4 and DR5. In addition, FLICE-like inhibitory protein (c-FLIP) protein is decreased. MG-132 treatment increases binding of DR5 to the adaptor protein FADD, and causes caspase-8 activation and cleavage of pro-apoptotic BID. Moreover, DR4:Fc or blockage of DR4 and DR5 expression using RNA interference, which prevents TRAIL apoptotic signaling, blocks proteasome inhibitor induced apoptosis. MG-132 also increases apoptosis and DR5 expression in normal B-cells. However, when the proteasome inhibitors are combined with TRAIL or TRAIL receptor activating antibodies the amount of apoptosis is increased in CLL cells but not in normal B cells. Thus, activation of the TRAIL apoptotic pathway contributes to proteasome inhibitor induced apoptosis in CLL cells. SN - 1360-8185 UR - https://www.unboundmedicine.com/medline/citation/16699949/The_TRAIL_apoptotic_pathway_mediates_proteasome_inhibitor_induced_apoptosis_in_primary_chronic_lymphocytic_leukemia_cells_ L2 - https://doi.org/10.1007/s10495-006-8048-9 DB - PRIME DP - Unbound Medicine ER -