Inhibitions of protein kinase C and proto-oncogene expressions in NIH 3T3 cells by apigenin.
Apigenin, a low-toxic and non-mutagenic plant flavonoid, suppresses 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-mediated tumour promotion of mouse skin. TPA has the ability to activate protein kinase C (PKC) and induce proto-oncogene expression. Our study shows that apigenin inhibits PKC by competing with ATP, and exhibits an IC50 value of 10 +/- 0.5 microM. Apigenin also reduces the level of TPA-stimulated phosphorylation of cellular proteins. Of the protein tyrosine kinases tested, the fibroblast growth factor (FGF) receptor was most strongly affected by apigenin (IC50 20 microM), and pp60v-src most weakly affected (IC50 > 200 microM). Treatment of NIH 3T3 cells with 100 ng/ml TPA and 10, 50 and 100 microM apigenin resulted in 50, 80 and 100% suppression of TPA-induced C-JUN expression, respectively. Treatment of TPA with 10 microM apigenin inhibited TPA-induced C-FOS expression. TPA-stimulated cell growth was suppressed by 25 microM apigenin. Our results provide some evidence for understanding apigenin's inhibitory effects of TPA-mediated tumour promotion.
Huang
Y T
YT
Institute of Biochemistry, College of Medicine, National Taiwan University 1, Republic of China.
Kuo
M L
ML
Liu
J Y
JY
Huang
S Y
SY
Lin
J K
JK
D016475:3T3 Cells / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D020843:Chamomile; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D009822:Oils, Volatile / Q000494:pharmacology*; D010766:Phosphorylation; D010946:Plants, Medicinal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D005419:Flavonoids; D009822:Oils, Volatile; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate