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Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines.
Br J Haematol. 2003 Dec; 123(5):921-32.BJ

Abstract

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively kills tumour cells but not normal cells. We investigated TRAIL sensitivity and the TRAIL-induced apoptosis signalling pathway in a panel of B-lymphocytic leukaemia cell lines. Depending upon TRAIL sensitivity, leukaemia cells could be divided into three groups: highly sensitive, moderately sensitive and resistant. TRAIL receptor-2 (DR5) plays an important role in transducing apoptosis signals. DR5 was internalized into the cytoplasm where it recruited FAS-associated death domain protein (FADD) under TRAIL stimulation in both sensitive and resistant cells. However, the active form of caspase-8 was recruited to FADD and only sensitive cells showed increased caspase-8 activity upon TRAIL stimulation. The caspase-8 specific inhibitor, Z-IETD, impaired caspase-8 activation and completely abrogated TRAIL-induced apoptosis. These results suggest that TRAIL resistance in B-lymphocytic leukaemia cells is due to negative regulation at the level of caspase-8 activation and that caspase-8 activation is an indispensable process in TRAIL-induced apoptosis. However, FADD-like interleukin-1 beta-converting enzyme inhibitory protein (c-FLIPL) was similarly expressed and down-regulated after TRAIL stimulation in both sensitive and resistant cells. Interestingly, in some cell lines, TRAIL sensitivity and caspase-8 activity was enhanced or restored with the treatment of cycloheximide (CHX). In addition, X-linked inhibitor of apoptosis (XIAP) levels decreased significantly and rapidly following treatment with CHX. Down-regulation of XIAP may be responsible for enhancement or restoration of TRAIL sensitivity after CHX treatment in B-lymphocytic leukaemia cells.

Authors+Show Affiliations

Department of Pediatrics, Mie University School of Medicine, Tsu, Mie, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14632785

Citation

Kang, Jian, et al. "Chemical Sensitization and Regulation of TRAIL-induced Apoptosis in a Panel of B-lymphocytic Leukaemia Cell Lines." British Journal of Haematology, vol. 123, no. 5, 2003, pp. 921-32.
Kang J, Kisenge RR, Toyoda H, et al. Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines. Br J Haematol. 2003;123(5):921-32.
Kang, J., Kisenge, R. R., Toyoda, H., Tanaka, S., Bu, J., Azuma, E., & Komada, Y. (2003). Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines. British Journal of Haematology, 123(5), 921-32.
Kang J, et al. Chemical Sensitization and Regulation of TRAIL-induced Apoptosis in a Panel of B-lymphocytic Leukaemia Cell Lines. Br J Haematol. 2003;123(5):921-32. PubMed PMID: 14632785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemical sensitization and regulation of TRAIL-induced apoptosis in a panel of B-lymphocytic leukaemia cell lines. AU - Kang,Jian, AU - Kisenge,Rodrick R, AU - Toyoda,Hidemi, AU - Tanaka,Shigeki, AU - Bu,Jun, AU - Azuma,Eiichi, AU - Komada,Yoshihiro, PY - 2003/11/25/pubmed PY - 2004/1/24/medline PY - 2003/11/25/entrez SP - 921 EP - 32 JF - British journal of haematology JO - Br J Haematol VL - 123 IS - 5 N2 - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively kills tumour cells but not normal cells. We investigated TRAIL sensitivity and the TRAIL-induced apoptosis signalling pathway in a panel of B-lymphocytic leukaemia cell lines. Depending upon TRAIL sensitivity, leukaemia cells could be divided into three groups: highly sensitive, moderately sensitive and resistant. TRAIL receptor-2 (DR5) plays an important role in transducing apoptosis signals. DR5 was internalized into the cytoplasm where it recruited FAS-associated death domain protein (FADD) under TRAIL stimulation in both sensitive and resistant cells. However, the active form of caspase-8 was recruited to FADD and only sensitive cells showed increased caspase-8 activity upon TRAIL stimulation. The caspase-8 specific inhibitor, Z-IETD, impaired caspase-8 activation and completely abrogated TRAIL-induced apoptosis. These results suggest that TRAIL resistance in B-lymphocytic leukaemia cells is due to negative regulation at the level of caspase-8 activation and that caspase-8 activation is an indispensable process in TRAIL-induced apoptosis. However, FADD-like interleukin-1 beta-converting enzyme inhibitory protein (c-FLIPL) was similarly expressed and down-regulated after TRAIL stimulation in both sensitive and resistant cells. Interestingly, in some cell lines, TRAIL sensitivity and caspase-8 activity was enhanced or restored with the treatment of cycloheximide (CHX). In addition, X-linked inhibitor of apoptosis (XIAP) levels decreased significantly and rapidly following treatment with CHX. Down-regulation of XIAP may be responsible for enhancement or restoration of TRAIL sensitivity after CHX treatment in B-lymphocytic leukaemia cells. SN - 0007-1048 UR - https://www.unboundmedicine.com/medline/citation/14632785/Chemical_sensitization_and_regulation_of_TRAIL_induced_apoptosis_in_a_panel_of_B_lymphocytic_leukaemia_cell_lines_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-1048&date=2003&volume=123&issue=5&spage=921 DB - PRIME DP - Unbound Medicine ER -