Matches in SemOpenAlex for { <https://semopenalex.org/work/W1567484625> ?p ?o ?g. }
Showing items 1 to 92 of
92
with 100 items per page.
- W1567484625 endingPage "2270" @default.
- W1567484625 startingPage "2270" @default.
- W1567484625 abstract "2270 TLK199 (ezatiostat hydrochloride) is a novel glutathione analog inhibitor of the enzyme glutathione S-transferase P1-1 (GST P1-1) that is currently under investigation for the treatment of cytopenias due to myelodysplastic syndrome or chemotherapy. GST P1-1 has been shown to negatively regulate JNK activity and decrease cellular reactive oxygen species (ROS) levels. Since both JNK activity and ROS levels have a role in cell proliferation, differentiation and apoptosis, a GST P1-1 inhibitor may modulate these cellular processes. Previously we have reported that TLK199 stimulates colony formation from normal peripheral blood and bone marrow cells at non-cytotoxic doses. In this study, we investigated additional effects of TLK199 on the growth of TF-1 erythroleukemia and HL-60 promyelocytic cells. Treatment with TLK199 in these leukemia cell lines resulted in apoptosis and increase in ROS levels. JNK activation was observed in TF-1 but not HL-60 cells. Consistent with the induction of apoptosis, treatment with TLK199 resulted in cleavage of PARP protein in a dose- and time-dependent manner, indicating the activation of caspase 3. In HL-60 cells, caspase 3 was maximally induced by 40 μM TLK199 in 5.5 hours, and its activation resulted in degradation of anti-apoptotic Mcl-1 protein. Treatment with TLK199 led to a loss of mitochondrial membrane potential and activation of caspase 9, but not caspase 8, suggesting that TLK199 induced the intrinsic apoptotic pathway. In support of the caspase cascade leading to loss of cell viability by TLK199, the pan-caspase inhibitor z-VAD-FMK protected HL-60 cells from undergoing apoptosis in the presence of TLK199 and increased the cytotoxic concentration of TLK199 by 2.5-fold. Microarray analysis of gene expression in TF-1 and HL-60 cells was performed. In both cell lines, TLK199 treatment resulted in the upregulation of several genes involved in the cellular response to ER stress. Consistent with the activation of JNK in TF-1 cells, TLK199 treatment upregulated genes for AP-1 transcription factors such as c- jun . These data indicate that TLK199 induces apoptosis in human leukemia cell lines TF-1 and HL-60 by activation of the caspase cascade and that caspase activation mediates the cytotoxic effects of TLK199." @default.
- W1567484625 created "2016-06-24" @default.
- W1567484625 creator A5006856205 @default.
- W1567484625 creator A5007396238 @default.
- W1567484625 creator A5010147176 @default.
- W1567484625 creator A5033226354 @default.
- W1567484625 creator A5050290665 @default.
- W1567484625 creator A5076751098 @default.
- W1567484625 creator A5087963156 @default.
- W1567484625 date "2008-05-01" @default.
- W1567484625 modified "2023-09-27" @default.
- W1567484625 title "Induction of apoptosis by TLK199 in human leukemia cells" @default.
- W1567484625 hasPublicationYear "2008" @default.
- W1567484625 type Work @default.
- W1567484625 sameAs 1567484625 @default.
- W1567484625 citedByCount "0" @default.
- W1567484625 crossrefType "journal-article" @default.
- W1567484625 hasAuthorship W1567484625A5006856205 @default.
- W1567484625 hasAuthorship W1567484625A5007396238 @default.
- W1567484625 hasAuthorship W1567484625A5010147176 @default.
- W1567484625 hasAuthorship W1567484625A5033226354 @default.
- W1567484625 hasAuthorship W1567484625A5050290665 @default.
- W1567484625 hasAuthorship W1567484625A5076751098 @default.
- W1567484625 hasAuthorship W1567484625A5087963156 @default.
- W1567484625 hasConcept C12519072 @default.
- W1567484625 hasConcept C153911025 @default.
- W1567484625 hasConcept C181199279 @default.
- W1567484625 hasConcept C185592680 @default.
- W1567484625 hasConcept C190283241 @default.
- W1567484625 hasConcept C203014093 @default.
- W1567484625 hasConcept C2776601000 @default.
- W1567484625 hasConcept C2778461978 @default.
- W1567484625 hasConcept C2781121885 @default.
- W1567484625 hasConcept C31573885 @default.
- W1567484625 hasConcept C48349386 @default.
- W1567484625 hasConcept C502942594 @default.
- W1567484625 hasConcept C538909803 @default.
- W1567484625 hasConcept C54355233 @default.
- W1567484625 hasConcept C55493867 @default.
- W1567484625 hasConcept C81885089 @default.
- W1567484625 hasConcept C86803240 @default.
- W1567484625 hasConcept C95444343 @default.
- W1567484625 hasConcept C98424977 @default.
- W1567484625 hasConceptScore W1567484625C12519072 @default.
- W1567484625 hasConceptScore W1567484625C153911025 @default.
- W1567484625 hasConceptScore W1567484625C181199279 @default.
- W1567484625 hasConceptScore W1567484625C185592680 @default.
- W1567484625 hasConceptScore W1567484625C190283241 @default.
- W1567484625 hasConceptScore W1567484625C203014093 @default.
- W1567484625 hasConceptScore W1567484625C2776601000 @default.
- W1567484625 hasConceptScore W1567484625C2778461978 @default.
- W1567484625 hasConceptScore W1567484625C2781121885 @default.
- W1567484625 hasConceptScore W1567484625C31573885 @default.
- W1567484625 hasConceptScore W1567484625C48349386 @default.
- W1567484625 hasConceptScore W1567484625C502942594 @default.
- W1567484625 hasConceptScore W1567484625C538909803 @default.
- W1567484625 hasConceptScore W1567484625C54355233 @default.
- W1567484625 hasConceptScore W1567484625C55493867 @default.
- W1567484625 hasConceptScore W1567484625C81885089 @default.
- W1567484625 hasConceptScore W1567484625C86803240 @default.
- W1567484625 hasConceptScore W1567484625C95444343 @default.
- W1567484625 hasConceptScore W1567484625C98424977 @default.
- W1567484625 hasLocation W15674846251 @default.
- W1567484625 hasOpenAccess W1567484625 @default.
- W1567484625 hasPrimaryLocation W15674846251 @default.
- W1567484625 hasRelatedWork W1445879316 @default.
- W1567484625 hasRelatedWork W2004427787 @default.
- W1567484625 hasRelatedWork W2036864615 @default.
- W1567484625 hasRelatedWork W2047161358 @default.
- W1567484625 hasRelatedWork W2047561468 @default.
- W1567484625 hasRelatedWork W2063902183 @default.
- W1567484625 hasRelatedWork W2075127177 @default.
- W1567484625 hasRelatedWork W2080156151 @default.
- W1567484625 hasRelatedWork W2130290736 @default.
- W1567484625 hasRelatedWork W2135405019 @default.
- W1567484625 hasRelatedWork W2143914529 @default.
- W1567484625 hasRelatedWork W2163890769 @default.
- W1567484625 hasRelatedWork W2297394833 @default.
- W1567484625 hasRelatedWork W2319498606 @default.
- W1567484625 hasRelatedWork W2322548654 @default.
- W1567484625 hasRelatedWork W2557053971 @default.
- W1567484625 hasRelatedWork W2557550124 @default.
- W1567484625 hasRelatedWork W2737544913 @default.
- W1567484625 hasRelatedWork W2792884505 @default.
- W1567484625 hasRelatedWork W2891583783 @default.
- W1567484625 hasVolume "68" @default.
- W1567484625 isParatext "false" @default.
- W1567484625 isRetracted "false" @default.
- W1567484625 magId "1567484625" @default.
- W1567484625 workType "article" @default.