Inhibitions of protein kinase C and proto-oncogene expressions in NIH 3T3 cells by apigenin
Inhibitions of protein kinase C and proto-oncogene expressions in NIH 3T3 cells by apigenin
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DOI：
10.1016/0959-8049(95)00540-4
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发表时间：
1996-01-01
影响因子：
8.4
通讯作者：
Lin, JK
中科院分区：
文献类型：
--
作者：
Huang, YT;Kuo, ML;Lin, JK
芹菜素是一种低毒、非诱变的植物黄酮类化合物，可抑制12-O-十四酰佛波醇-13-乙酸酯(TPA)介导的小鼠皮肤肿瘤促进作用。TPA具有激活蛋白激酶C(PKC)、诱导原癌基因表达的功能。我们的研究表明，芹菜素通过与ATP竞争抑制PKC，其IC50值为10+/-0.5mM。芹菜素还降低了TPA刺激的细胞蛋白的磷酸化水平。在所检测的蛋白酪氨酸激酶中，成纤维细胞生长因子受体受芹菜素的影响最强(IC50为20 mU)，而pp60(v-src)的作用最弱(IC50和GT；200 mU M)。100 ng/mlTPA和10、50、100 mU的芹菜素处理NIH3T3细胞后，TPA诱导的C-jun表达分别被抑制50%、80%和100%。10 mU/L的芹菜素处理TPA可抑制TPA诱导的C-fos表达。25 mU的芹菜素抑制TPA刺激的细胞生长。我们的结果为理解芹菜素对TPA介导的促肿瘤作用的抑制作用提供了一些证据。
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 mu M. 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 mu M), and pp60(v-src) most weakly affected (IC50 > 200 mu M). Treatment of NIH 3T3 cells with 100 ng/ml TPA and 10, 50 and 100 mu M apigenin resulted in 50, 80 and 100% suppression of TPA-induced C-JUN expression, respectively. Treatment of TPA with 10 (mu M apigenin inhibited TPA-induced C-FOS expression. TPA-stimulated cell growth was suppressed by 25 mu M apigenin. Our results provide some evidence for understanding apigenin's inhibitory effects of TPA-mediated tumour promotion.