Roles of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in apoptosis of human monoblastic leukemia U937 cells by lectin-II isolated from Korean mistletoe.
The mitogen-activated protein kinase (MAPK) family members have been implicated in cell survival. We have previously demonstrated that cytotoxic lectin-II isolated from Korean mistletoe induces apoptotic cell death in the human monoblastic leukemia cell line, U937, via the activation of the stress-activated protein kinases/c-Jun N-terminal kinase (SAPK/JNK). In the present study, the roles of extracellular signal-regulated kinases (ERK1/2) and p38 MAPK in lectin-II-induced apoptosis have been investigated. Treatment of U937 cells with lectin-II resulted in apoptotic DNA fragmentation, which was preceded by the activation of ERK1/2, p38 MAPK and SAPK/JNK. This lectin-II-induced DNA fragmentation was significantly enhanced when ERK1/2 activation was selectively inhibited by PD098059. 12-O-tetradecanoylphorbol-13-acetate, which stimulates ERK activity in U937 cells, markedly reduced lectin-II-induced DNA fragmentation. Inhibition of p38 MAPK activity with p38-specific inhibitor, SB203580, partially inhibited lectin-II-induced DNA fragmentation. These results suggest that ERK1/2 and p38 MAPK may have opposite effects on cell survival in response to cytotoxic mistletoe lectin-II, which may contribute to the modulation of lectin-II-mediated cytotoxic activity.
Pae
H O
HO
Medicinal Resources Research Center, Wonkwang University, Iksan, Chonbug 570-749, South Korea.
Oh
G S
GS
Kim
N Y
NY
Shin
M K
MK
Lee
H S
HS
Yun
Y G
YG
Oh
H
H
Kim
Y M
YM
Chung
H T
HT
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism; D014784:Mistletoe; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D028321:Plant Preparations; D010940:Plant Proteins; D011725:Pyridines / Q000494:pharmacology; D054790:Ribosome Inactivating Proteins, Type 2; D015398:Signal Transduction / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology*; D020298:U937 Cells / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D005419:Flavonoids; D007093:Imidazoles; D028321:Plant Preparations; D010940:Plant Proteins; D011725:Pyridines; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one