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Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells.
Blood. 2000 Dec 01; 96(12):3900-6.Blood

Abstract

In present studies, treatment with tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL, also known as Apo-2 ligand [Apo-2L]) is shown to induce apoptosis of the human acute leukemia HL-60, U937, and Jurkat cells in a dose-dependent manner, with the maximum effect seen following treatment of Jurkat cells with 0.25 microg/mL of Apo-2L (95.0% +/- 3.5% of apoptotic cells). Susceptibility of these acute leukemia cell types, which are known to lack p53(wt) function, did not appear to correlate with the levels of the apoptosis-signaling death receptors (DRs) of Apo-2L, ie, DR4 and DR5; decoy receptors (DcR1 and 2); FLAME-1 (cFLIP); or proteins in the inhibitors of apoptosis proteins (IAP) family. Apo-2L-induced apoptosis was associated with the processing of caspase-8, Bid, and the cytosolic accumulation of cytochrome c as well as the processing of caspase-9 and caspase-3. Apo-2L-induced apoptosis was significantly inhibited in HL-60 cells that overexpressed Bcl-2 or Bcl-x(L). Cotreatment with either a caspase-8 or a caspase-9 inhibitor suppressed Apo-2L-induced apoptosis. Treatment of human leukemic cells with etoposide, Ara-C, or doxorubicin increased DR5 but not DR4, Fas, DcR1, DcR2, Fas ligand, or Apo-2L levels. Importantly, sequential treatment of HL-60 cells with etoposide, Ara-C, or doxorubicin followed by Apo-2L induced significantly more apoptosis than treatment with Apo-2L, etoposide, doxorubicin, or Ara-C alone, or cotreatment with Apo-2L and the antileukemic drugs, or treatment with the reverse sequence of Apo-2L followed by one of the antileukemic drugs. These findings indicate that treatment with etoposide, Ara-C, or doxorubicin up-regulates DR5 levels in a p53-independent manner and sensitizes human acute leukemia cells to Apo-2L-induced apoptosis. (Blood. 2000;96:3900-3906)

Authors+Show Affiliations

Division of Clinical and Translational Research, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11090076

Citation

Wen, J, et al. "Antileukemic Drugs Increase Death Receptor 5 Levels and Enhance Apo-2L-induced Apoptosis of Human Acute Leukemia Cells." Blood, vol. 96, no. 12, 2000, pp. 3900-6.
Wen J, Ramadevi N, Nguyen D, et al. Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells. Blood. 2000;96(12):3900-6.
Wen, J., Ramadevi, N., Nguyen, D., Perkins, C., Worthington, E., & Bhalla, K. (2000). Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells. Blood, 96(12), 3900-6.
Wen J, et al. Antileukemic Drugs Increase Death Receptor 5 Levels and Enhance Apo-2L-induced Apoptosis of Human Acute Leukemia Cells. Blood. 2000 Dec 1;96(12):3900-6. PubMed PMID: 11090076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells. AU - Wen,J, AU - Ramadevi,N, AU - Nguyen,D, AU - Perkins,C, AU - Worthington,E, AU - Bhalla,K, PY - 2000/11/23/pubmed PY - 2001/2/28/medline PY - 2000/11/23/entrez SP - 3900 EP - 6 JF - Blood JO - Blood VL - 96 IS - 12 N2 - In present studies, treatment with tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL, also known as Apo-2 ligand [Apo-2L]) is shown to induce apoptosis of the human acute leukemia HL-60, U937, and Jurkat cells in a dose-dependent manner, with the maximum effect seen following treatment of Jurkat cells with 0.25 microg/mL of Apo-2L (95.0% +/- 3.5% of apoptotic cells). Susceptibility of these acute leukemia cell types, which are known to lack p53(wt) function, did not appear to correlate with the levels of the apoptosis-signaling death receptors (DRs) of Apo-2L, ie, DR4 and DR5; decoy receptors (DcR1 and 2); FLAME-1 (cFLIP); or proteins in the inhibitors of apoptosis proteins (IAP) family. Apo-2L-induced apoptosis was associated with the processing of caspase-8, Bid, and the cytosolic accumulation of cytochrome c as well as the processing of caspase-9 and caspase-3. Apo-2L-induced apoptosis was significantly inhibited in HL-60 cells that overexpressed Bcl-2 or Bcl-x(L). Cotreatment with either a caspase-8 or a caspase-9 inhibitor suppressed Apo-2L-induced apoptosis. Treatment of human leukemic cells with etoposide, Ara-C, or doxorubicin increased DR5 but not DR4, Fas, DcR1, DcR2, Fas ligand, or Apo-2L levels. Importantly, sequential treatment of HL-60 cells with etoposide, Ara-C, or doxorubicin followed by Apo-2L induced significantly more apoptosis than treatment with Apo-2L, etoposide, doxorubicin, or Ara-C alone, or cotreatment with Apo-2L and the antileukemic drugs, or treatment with the reverse sequence of Apo-2L followed by one of the antileukemic drugs. These findings indicate that treatment with etoposide, Ara-C, or doxorubicin up-regulates DR5 levels in a p53-independent manner and sensitizes human acute leukemia cells to Apo-2L-induced apoptosis. (Blood. 2000;96:3900-3906) SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/11090076/Antileukemic_drugs_increase_death_receptor_5_levels_and_enhance_Apo_2L_induced_apoptosis_of_human_acute_leukemia_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)48234-5 DB - PRIME DP - Unbound Medicine ER -