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

• 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
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-008-0037-z

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.