The p38 pathway inhibitor SB202190 activates MEK/MAPK to stimulate the growth of leukemia cells.
In this study, the biological effects of signal transduction inhibitors on leukemia cells were examined. We found that the p38 inhibitor SB202190 enhanced the growth of THP-1 and MV4-11 cells. To determine the pathway affected by SB202190, we examined the 50% effective dose (ED(50)) values for THP-1 cell growth in combination with several inhibitors. In the presence of SB202190, the ED(50) values for the farnesyltransferase inhibitor FPT inhibitor II and MEK inhibitor U0126 were significantly decreased. Western blot analysis revealed that SB202190 increased the phosphorylation of C-Raf and extracellular regulated kinase (ERK), suggesting that Ras-Raf-MEK-mitogen-activated protein kinase (MAPK) pathway activation is involved in the leukemia cell growth induced by SB202190.
Hirosawa
Megumi
M
Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, Japan.
Nakahara
Masako
M
Otosaka
Risa
R
Imoto
Akemi
A
Okazaki
Toshio
T
Takahashi
Shinichiro
S
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D017931:DNA Primers; D004789:Enzyme Activation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D017931:DNA Primers; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole