[Indomethacin-induced HL-60 leukemic cell apoptosis and the activation of C-jun NH2- terminal kinase signal transduction pathway].
OBJECTIVE
To observe the effect of indomethacin on inhibiting the proliferation of HL-60 cells and inducing HL-60 cells apoptosis and to explore the activation of C-Jun NH2-terminal kinase (JNK) signal transduction pathway in mediating indomethacin-induced HL-60 cell apoptosis.


METHODS
The cell viability was determined by Trypan blue staining and the state of cell proliferation was analyzed; DNA ladder pattern and AO/EB staining were applied to identify the cell apoptosis; the apoptotic signal proteins including caspase-9, caspase-3, and PARP and the proteins of JNK signal pathway such as MEK4, JNK, P-JNK, and P-C-Jun, were detected by Western blotting.


RESULTS
Indomethacin at 200 to approximately 400 micromol significantly inhibited the proliferation of HL-60 cells and induced the cell apoptosis in a time- or concentration-dependent manner; caspase-9, caspase-3, and PARP were cleaved and activated in undergoing apoptotic cells; and the expressions of MEK4, P-JNK, and P-C-Jun were upregulated with the increase of indomethacin concentration.


CONCLUSIONS
Indomethacin can inhibit the proliferation of HL-60 cell and induce leukemic cell apoptosis. The activation of JNK signal transduction pathway mediates the event of indomethacin-induced HL-60 cell apoptosis. JNK signal pathway is located in the upstream of caspase signal pathway.
Zhang
Guang-sen
GS
Department of Haematology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Liu
Ding-sheng
DS
Xia
Meng
M
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction
D048031:JNK Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D007213:Indomethacin