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Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo-2L/tumor necrosis factor-related apoptosis inducing ligand-induced death inducing signaling complex activity and apoptosis of human acute leukemia cells.
Cancer Res. 2004 Apr 01; 64(7):2580-9.CR

Abstract

Present studies demonstrate that treatment with the histone deacetylases inhibitor LAQ824, a cinnamic acid hydroxamate, increased the acetylation of histones H3 and H4, as well as induced p21(WAF1) in the human T-cell acute leukemia Jurkat, B lymphoblast SKW 6.4, and acute myelogenous leukemia HL-60 cells. This was associated with increased accumulation of the cells in the G(1) phase of the cell cycle, as well as accompanied by the processing and activity of caspase-9 and -3, and apoptosis. Exposure to LAQ824 increased the mRNA and protein expressions of the death receptors DR5 and/or DR4, but reduced the mRNA and protein levels of cellular FLICE-inhibitory protein (c-FLIP). As compared with treatment with Apo-2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or LAQ824 alone, pretreatment with LAQ824 increased the assembly of Fas-associated death domain and caspase-8, but not of c-FLIP, into the Apo-2L/TRAIL-induced death-inducing signaling complex. This increased the processing of caspase-8 and Bcl-2 interacting domain (BID), augmented cytosolic accumulation of the prodeath molecules cytochrome-c, Smac and Omi, as well as led to increased activity of caspase-3 and apoptosis. Treatment with LAQ824 also down-regulated the levels of Bcl-2, Bcl-x(L), XIAP, and survivin. Partial inhibition of apoptosis due to LAQ824 or Apo-2L/TRAIL exerted by Bcl-2 overexpression was reversed by cotreatment with LAQ824 and Apo-2L/TRAIL. Significantly, cotreatment with LAQ824 increased Apo-2L/TRAIL-induced apoptosis of primary acute myelogenous leukemia blast samples isolated from 10 patients with acute myelogenous leukemia. Taken together, these findings indicate that LAQ824 may have promising activity in augmenting Apo-2L/TRAIL-induced death-inducing signaling complex and apoptosis of human acute leukemia cells.

Authors+Show Affiliations

Department of Interdisciplinary Oncology, Moffitt Cancer Center and Research Institute University of South Florida, Tampa, Florida 33612, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

15059915

Citation

Guo, Fei, et al. "Cotreatment With Histone Deacetylase Inhibitor LAQ824 Enhances Apo-2L/tumor Necrosis Factor-related Apoptosis Inducing Ligand-induced Death Inducing Signaling Complex Activity and Apoptosis of Human Acute Leukemia Cells." Cancer Research, vol. 64, no. 7, 2004, pp. 2580-9.
Guo F, Sigua C, Tao J, et al. Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo-2L/tumor necrosis factor-related apoptosis inducing ligand-induced death inducing signaling complex activity and apoptosis of human acute leukemia cells. Cancer Res. 2004;64(7):2580-9.
Guo, F., Sigua, C., Tao, J., Bali, P., George, P., Li, Y., Wittmann, S., Moscinski, L., Atadja, P., & Bhalla, K. (2004). Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo-2L/tumor necrosis factor-related apoptosis inducing ligand-induced death inducing signaling complex activity and apoptosis of human acute leukemia cells. Cancer Research, 64(7), 2580-9.
Guo F, et al. Cotreatment With Histone Deacetylase Inhibitor LAQ824 Enhances Apo-2L/tumor Necrosis Factor-related Apoptosis Inducing Ligand-induced Death Inducing Signaling Complex Activity and Apoptosis of Human Acute Leukemia Cells. Cancer Res. 2004 Apr 1;64(7):2580-9. PubMed PMID: 15059915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cotreatment with histone deacetylase inhibitor LAQ824 enhances Apo-2L/tumor necrosis factor-related apoptosis inducing ligand-induced death inducing signaling complex activity and apoptosis of human acute leukemia cells. AU - Guo,Fei, AU - Sigua,Celia, AU - Tao,Jianguo, AU - Bali,Purva, AU - George,Prince, AU - Li,Yunqing, AU - Wittmann,Sylvie, AU - Moscinski,Lynn, AU - Atadja,Peter, AU - Bhalla,Kapil, PY - 2004/4/3/pubmed PY - 2004/5/20/medline PY - 2004/4/3/entrez SP - 2580 EP - 9 JF - Cancer research JO - Cancer Res VL - 64 IS - 7 N2 - Present studies demonstrate that treatment with the histone deacetylases inhibitor LAQ824, a cinnamic acid hydroxamate, increased the acetylation of histones H3 and H4, as well as induced p21(WAF1) in the human T-cell acute leukemia Jurkat, B lymphoblast SKW 6.4, and acute myelogenous leukemia HL-60 cells. This was associated with increased accumulation of the cells in the G(1) phase of the cell cycle, as well as accompanied by the processing and activity of caspase-9 and -3, and apoptosis. Exposure to LAQ824 increased the mRNA and protein expressions of the death receptors DR5 and/or DR4, but reduced the mRNA and protein levels of cellular FLICE-inhibitory protein (c-FLIP). As compared with treatment with Apo-2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or LAQ824 alone, pretreatment with LAQ824 increased the assembly of Fas-associated death domain and caspase-8, but not of c-FLIP, into the Apo-2L/TRAIL-induced death-inducing signaling complex. This increased the processing of caspase-8 and Bcl-2 interacting domain (BID), augmented cytosolic accumulation of the prodeath molecules cytochrome-c, Smac and Omi, as well as led to increased activity of caspase-3 and apoptosis. Treatment with LAQ824 also down-regulated the levels of Bcl-2, Bcl-x(L), XIAP, and survivin. Partial inhibition of apoptosis due to LAQ824 or Apo-2L/TRAIL exerted by Bcl-2 overexpression was reversed by cotreatment with LAQ824 and Apo-2L/TRAIL. Significantly, cotreatment with LAQ824 increased Apo-2L/TRAIL-induced apoptosis of primary acute myelogenous leukemia blast samples isolated from 10 patients with acute myelogenous leukemia. Taken together, these findings indicate that LAQ824 may have promising activity in augmenting Apo-2L/TRAIL-induced death-inducing signaling complex and apoptosis of human acute leukemia cells. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15059915/Cotreatment_with_histone_deacetylase_inhibitor_LAQ824_enhances_Apo_2L/tumor_necrosis_factor_related_apoptosis_inducing_ligand_induced_death_inducing_signaling_complex_activity_and_apoptosis_of_human_acute_leukemia_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15059915 DB - PRIME DP - Unbound Medicine ER -