Tumor necrosis factor-α enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway

The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-α, interleukin-4, t...

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Bibliographic Details
Published in:International journal of hematology 2008-03, Vol.87 (2), p.189-194
Main Authors: Yu, Hong-Nu, Lee, Young-Rae, Noh, Eun-Mi, Lee, Kyung-Sun, Song, Eun-Kyung, Han, Myung-Kwan, Lee, Yong-Chul, Yim, Chang-Yeol, Park, Jinny, Kim, Byeong-Soo, Lee, Sung-Ho, Lee, Seung Jin, Kim, Jong-Suk
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Differentiation - drug effects
Dimethyl Sulfoxide - pharmacology
Drug Synergism
Drug Therapy, Combination
Granulocyte Precursor Cells - drug effects
Hematologic and hematopoietic diseases
Hematology
HL-60 Cells
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
MAP Kinase Signaling System - drug effects
Medical sciences
Medicine
Medicine & Public Health
Mitogen-Activated Protein Kinase 1 - drug effects
Mitogen-Activated Protein Kinase 3 - drug effects
Oncology
Original Article
Phosphorylation - drug effects
Tumor Necrosis Factor-alpha - pharmacology
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Summary:The differentiation of promyelocytic leukemic cells into mature cells is the major strategy for drug-based treatment of leukemia. Higher efficient methods to differentiate promyelocytic leukemic cells have been developed using various differentiation inducers including interferon-α, interleukin-4, tumor necrosis factor-α (TNF-α), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-α with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-α enhanced CD11b expression and percent of cell population in the G 1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-α in combination with DMSO on HL-60 differentiation, but the inhibition NF-κB pathway did not. These results suggest that TNF-α synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway.
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-008-0037-z