AI Article Synopsis

  • - The study investigated the effects of ITF2357, a histone deacetylase inhibitor, on HL-60 acute myeloid leukemia cells, revealing it causes significant cell growth inhibition and promotes apoptosis (cell death).
  • - ITF2357 decreased protein levels of anti-apoptotic factors (BCL-2, MCL-1, BCL-X) while increasing pro-apoptotic factors (BAK) without affecting NF-κB DNA binding activity.
  • - Microarray analysis identified several deregulated pathways related to inflammation and cell signaling, indicating ITF2357's potential for therapeutic applications in treating leukemia.

Article Abstract

Background: Cytotoxic and pro-apoptotic effects exerted by the histone deacetylase inhibitor ITF2357 have been reported in acute myeloid leukemia HL-60 cells. In the current study, its mechanism of action was investigated at the molecular level.

Materials And Methods: Cell proliferation was evaluated by methyl thiazol tetrazolium bromide reduction; apoptosis by annexin V, mitochondrial transmembrane potential by tetramethylrhodamine ethyl ester. Functional experiments and gene expression evaluations were performed by flow cytometry, microarray, and quantitative polymerase chain reaction.

Results: Significant cell growth inhibition and increased apoptosis were observed. ITF2357 reduced protein levels of BCL-2, MCL-1, and BCL-X, and increased levels of BAK. Exposure to ITF2357 did not abrogate NF-κB DNA binding. After microarray analysis, interleukin-10, interleukin-6, epidermal growth factor, peroxisome proliferator-activated receptor (PPAR), transforming growth factor β, P38 mitogen-activated protein kinase, aryl hydrocarbon receptor, xenobiotic metabolism, PPAR/retinoic acid receptor, NF-κB, apoptosis, lipopolysaccharide/interleukin-1, G-protein receptor, T-cell receptor, and platelet-derived growth factor were the de-regulated pathways.

Conclusion: This study shows that ITF2357 influences both proliferation and inflammatory pathways in HL-60 cells; this observation could have possible applications in clinical practice.

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