Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor

作者: Y -T Huang , J -J Hwang , P -P Lee , F -C Ke , J -H Huang

DOI: 10.1038/SJ.BJP.0702879

关键词:

摘要: 1. Flavonoids display a wide range of pharmacological properties including anti-inflammatory. Anti-mutagenic, anti-carcinogenic and anti-cancer effects. Here, we evaluated the effects eight flavonoids on tumour cell proliferation, cellular protein phosphorylation, matrix metalloproteinase (MMPs) secretion. 2. Of examined, luteolin (Lu) quercetin (Qu) were two most potent agents, significantly inhibited A431 proliferation with IC50 values 19 21 micronM, respectively. 3. The epidermal growth factor (EGF) (10 nM) promoted cells (+25+/-4.6%) mediated receptor (EGFR) tyrosine kinase activity autophosphorylation EGFR by Lu Qu. At concentration 20 both Qu markedly decreased levels phosphorylation proteins, EGFR. 4. treated or exhibited protuberant cytoplasmic blebs progressive shrinkage morphology. also time-dependently induced appearance ladder pattern DNA fragmentation, this effect was abolished EGF treatment. 5. addition only marginally diminished inhibitory rate cells, treatment proteins greatly reduced indicating may act effectively to inhibit kinases, kinase. 6. increased metalloproteinase-2 (MMP-2) metalloproteinase-9 (MMP-9), while appeared suppress secretion these MMPs in cells. 7. Examination relationship between chemical structure reveal that double bond C2 C3 ring C OH groups C3' C4' B are critical for biological activities. 8. This study demonstrates Qu, stimulatory EGF, MMP be at least partly through supports idea have potential as anti-metastasis agents.

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