Informace o publikaci
Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery
| Autoři | |
|---|---|
| Rok publikování | 2009 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | European Journal of Haematology |
| Fakulta / Pracoviště MU | |
| Citace | |
| Obor | Genetika a molekulární biologie |
| Klíčová slova | caspases; MAPK; MK886; NFkappaB; TNF-alpha |
| Popis | Acute myeloid leukemia cells can be cured by differentiating therapy, but it has side effects. A study of other differentiation signaling pathways is therefore useful. We demonstrated previously that the co-treatment of HL-60 cells with Tumor necrosis factor-a (TNF-a) (1 ng/mL) and inhibitor of 5-lipoxygenase MK886 (5 lM) potentiated both monocytic differentiation and apoptosis. In this study, we detected enhanced activation of three main types of MAPKs (p38, JNK, ERK). The inhibition of pro-apoptotic MAPKs (p38 and JNK) suppressed the effect of MK886 + TNF-a co-treatment. On the other hand, down-regulation of prosurvival ERK pathway led to increased differentiation. Those effects were accompanied by increased activation of caspases in cells treated by MK886 + TNF-a. Pan-caspase inhibitor ZVAD-fmk significantly decreased both number of apoptotic and differentiated cells. The same effect was observed after inhibition of caspase 9, but not caspase 3 and 8. |