Involvement of tumor necrosis factor (TNF-α) in arsenic trioxide induced apoptotic cell death of murine myeloid leukemia cells

Nai Ki MAK, Ricky N S WONG, K. N. Leung, M. C. Fung

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Arsenic trioxide (As2O3) has recently been shown to be effective to inhibit the growth and to induce apoptosis in acute promyelocytic leukemia (APL) but not in acute myeloid leukemia (AML) cells. Recently, we have isolated an As2O3 sensitive subclone JCS-16 from the murine myeloid leukemia WEHI 3B (JCS). At the concentrations of 0.3-3 μM, As2O3 induces a dose-dependent cytotoxicity and growth inhibition on the JCS-16 cells. As2O3 also induces apoptotic cell death, as judged by the presence of apoptotic nuclei, at 6 h after treatment. Morphological differentiation was not observed in As2O3 treated JCS cells. Neutralizing anti-TNF-α antibody was found to reduce the As2O3-mediated apoptotic cell death of JCS-16 cells. Growth inhibitory effect of As2O3 was also reduced after the addition of anti-TNF-α. In addition, reverse transcription polymerase chain reaction (RT-PCR) and reverse northern blot analysis demonstrated that the expression of TNF receptor (TNF-R2), IL-4, and IL-4R was down-regulate at 1 h after As2O3 treatment. The expression of TNF-α and TNF-R1 was not affected. Our results suggest that the autocrine action of TNF-α might play a role in As2O3-induced apoptotic cell death of JCS-16 leukemia cells.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalToxicology Letters
Volume135
Issue number1-2
DOIs
Publication statusPublished - 5 Sep 2002

Scopus Subject Areas

  • Toxicology

User-Defined Keywords

  • Arsenic trioxide
  • Myeloid leukemia
  • TNF-R
  • TNF-α

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