| 18256785 |
Yu HN, Lee YR, Noh EM, Lee KS, Song EK, Han MK, Lee YC, Yim CY, Park J, Kim BS, Lee SH, Lee SJ, Kim JS: Tumor necrosis factor-alpha enhances DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK pathway. Int J Hematol. 2008 Mar;87(2):189-94. Epub 2008 Feb 8.
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-alpha, interleukin-4, tumor necrosis factor-alpha (TNF-alpha), and dimethyl sulfoxide (DMSO) as a single agent or in combination with each other. Here, we show that a combination of TNF-alpha with DMSO shows a synergic effect on HL-60 cell differentiation through the activation of ERK pathway. TNF-alpha enhanced CD11b expression and percent of cell population in the G1 phase induced by DMSO, which are hallmarks for HL-60 cell differentiation. Inhibition of ERK pathway abolished the synergic effect of TNF-alpha in combination with DMSO on HL-60 differentiation, but the inhibition NF-kappaB pathway did not. These results suggest that TNF-alpha synergistically increases DMSO-induced differentiation of HL-60 cells through the activation of ERK/MAPK-signaling pathway. |
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