Involvement of tumor necrosis factor (TNF-alpha) in arsenic trioxide induced apoptotic cell death of murine myeloid leukemia cells.
Arsenic trioxide (As(2)O(3)) 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 As(2)O(3) sensitive subclone JCS-16 from the murine myeloid leukemia WEHI 3B (JCS). At the concentrations of 0.3-3 microM, As(2)O(3) induces a dose-dependent cytotoxicity and growth inhibition on the JCS-16 cells. As(2)O(3) also induces apoptotic cell death, as judged by the presence of apoptotic nuclei, at 6 h after treatment. Morphological differentiation was not observed in As(2)O(3) treated JCS cells. Neutralizing anti-TNF-alpha antibody was found to reduce the As(2)O(3)-mediated apoptotic cell death of JCS-16 cells. Growth inhibitory effect of As(2)O(3) was also reduced after the addition of anti-TNF-alpha. 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 As(2)O(3) treatment. The expression of TNF-alpha and TNF-R1 was not affected. Our results suggest that the autocrine action of TNF-alpha might play a role in As(2)O(3)-induced apoptotic cell death of JCS-16 leukemia cells.
Mak
N K
NK
Department of Biology, The Hong Kong Baptist University, Hong Kong, PR China. nkmak@hkbu.edu.hk
Wong
R N S
RN
Leung
K N
KN
Fung
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects*; D005562:Formazans / Q000737:chemistry; D015847:Interleukin-4 / Q000096:biosynthesis; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010087:Oxides / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D001152:Arsenicals; D005562:Formazans; D010087:Oxides; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D018124:Receptors, Tumor Necrosis Factor; D013778:Tetrazolium Salts; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C079782:MTT formazan; D000077237:Arsenic Trioxide