Publication details
Monocytic differentiation of leukemic HL-60 cells induced by co-treatment with TNF-alpha and MK886 requires activation of pro-apoptotic machinery
| Authors | |
|---|---|
| Year of publication | 2009 |
| Type | Article in Periodical |
| Magazine / Source | European Journal of Haematology |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Keywords | caspases; MAPK; MK886; NFkappaB; TNF-alpha |
| Description | 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. |