Baicalein inhibits Raf-1-mediated phosphorylation of MEK-1 in C6 rat glioma cells.
Baicalein is a flavonoid derived from the Scutellaria root. In investigations of the inhibitors of prostaglandin synthesis in C6 rat glioma cells, we found that baicalein had a potent inhibitory activity on prostaglandin synthesis induced by either histamine or A23187, a Ca(2+) ionophore. Baicalein inhibited histamine- or A23187-induced phosphorylation of p42/p44 extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK), which causes the phosphorylation of cytosolic phospholipase A(2) (PLA(2)). Baicalein also inhibited the phosphorylation of MAPK kinase-1 (MEK-1) induced by histamine or A23187 in the cells. To examine the site of action of baicalein, MEK-1 and Raf-1 were prepared by immunoprecipitation with anti-MEK-1 and anti-Raf-1 antibodies, respectively. Baicalein inhibited the phosphorylation of exogenous MEK-1 by Raf-1 under cell-free conditions, while it did not change the phosphorylation of exogenous p42 MAPK by MEK-1. These results imply that baicalein inhibits the ERK/MAPK cascade, acting on the phosphorylation of MEK-1 by Raf-1.
Nakahata
Norimichi
N
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. nakahata@mail.pharm.tohoku.ac.jp
Tsuchiya
Chikako
C
Nakatani
Keigo
K
Ohizumi
Yasushi
Y
Ohkubo
Satoko
S
D000818:Animals; D002474:Cell-Free System; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D005910:Glioma; D048369:MAP Kinase Kinase 1; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D011448:Prostaglandin Antagonists; C006680:baicalein; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one