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

Hong Nu Yu, Young Rae Lee, Eun Mi Noh, Kyung Sun Lee, Eun Kyung Song, Myung Kwan Han, Yong Chul Lee, Chang Yeol Yim, Jinny Park, Byeong Soo Kim, Sung Ho Lee, Seung Jin Lee, Jong Suk Kim

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20 Scopus citations

Abstract

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 G1 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.

Original languageEnglish
Pages (from-to)189-194
Number of pages6
JournalInternational Journal of Hematology
Volume87
Issue number2
DOIs
StatePublished - Mar 2008

Bibliographical note

Funding Information:
Acknowledgments This work was supported by grants of the Korea Science and Engineering Foundation (nos. R01-2002-000-00493-0, R11-2002-100-02007-0, and M10528010003-05N2801-00310) and the grant of Post Doc. Program, Chonbuk National University (K.-S. Lee).

Keywords

  • DMSO
  • Leukemic cell differentiation
  • MAPK
  • NF-κB
  • TNF-α

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