Green tea compounds inhibit tyrosine phosphorylation of PDGF beta-receptor and transformation of A172 human glioblastoma.
The effect of the green tea compounds 2-(3,4-dihydroxyphenyl)-3, 4-dihydro-2H-1-benzopyran-3,5,7-triol (catechin), epicathechin (EC), epigallocathechin-3 gallate (EGCG), epicathechin-3 gallate (ECG) and catechin-3 gallate (CG) on the tyrosine phosphorylation of PDGF beta-receptor (PDGF-Rbeta) and on the anchorage-independent growth of A172 glioblastoma cells in semisolid agar has been investigated. Treatment of A172 glioblastoma with 50 microM CG, ECG, EGCG and 25 microM Tyrphostin 1296 resulted in an 82+/-17%, 77+/-21%, 75+/-8% and 55+/-11%, respectively (mean+/-S.D., n=3) inhibition of the PDGF-BB-induced tyrosine phosphorylation of PDGF-Rbeta. The PDGF-Rbeta downstream intracellular transduction pathway including tyrosine phosphorylation of phospholipase C-gamma1 (PLC-gamma1) and phosphatidylinositol 3'-kinase (PI 3'-K) was also inhibited. Spheroid formation was completely inhibited by 50 microM ECG, CG, EGCG and by 25 microM Tyrphostin 1296. We conclude that catechins of the green tea possessing the gallate group in their chemical structure act as anticancer agents probably partly via their ability to suppress the tyrosine kinase activity of the PDGF-Rbeta.
Sachinidis
A
A
Medizinische Universitäts-Poliklinik, Wilhelmstr. 35-37, 53111, Bonn, Germany. sachinidis@uni-bonn.de
Seul
C
C
Seewald
S
S
Ahn
H
H
Ko
Y
Y
Vetter
H
H
D002392:Catechin / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D013662:Tea / Q000737:chemistry*; D014443:Tyrosine / Q000378:metabolism
D013662:Tea; D014443:Tyrosine; D002392:Catechin; D011505:Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta