Dietary Flavonoids Luteolin and Quercetin Inhibit Migration and Invasion of Squamous Carcinoma through Reduction of Src/Stat3/S100A7 Signaling
| Autor: | Kuen Haur Lee, Mau-Sun Chang, Cheng Wei Lin, Yu Lin A. Lee, Ku Chung Chen, Lang Ta Lee, Wen Hsien Hsu, Tzu Ping Ko, Jhen Jia Fan, Ming Ting Lee, Chia Hsiung Cheng |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry medicine.disease_cause Biochemistry Article quercetin 03 medical and health sciences chemistry.chemical_compound Transactivation 0302 clinical medicine medicine metastasis luteolin STAT3 Molecular Biology S100A7 biology Stat3 lcsh:RM1-950 food and beverages Cell Biology Squamous carcinoma lcsh:Therapeutics. Pharmacology 030104 developmental biology chemistry SU6656 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein Carcinogenesis Luteolin Proto-oncogene tyrosine-protein kinase Src Src |
| Zdroj: | Antioxidants Volume 8 Issue 11 Antioxidants, Vol 8, Iss 11, p 557 (2019) |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox8110557 |
| Popis: | Flavonoids are well-known antioxidants and have shown the ability to prevent tumor formation and recurrence. Especially in dietary flavonoids, they have provided convenience and consistence of intake for long-term prevention of tumor formation. Previous reports suggested that S100 calcium-binding protein A7 (S100A7) might activate epithelial&ndash mesenchymal transition (EMT) signaling and promote the metastasis of tumor cells however, the regulatory signaling was unclear. In this study, we found that S100A7 was highly expressed in cancer cells and could be reduced by luteolin (Lu) and quercetin (Qu) through Src/Stat3 signaling. We found that the protein levels of S100A7, phosphorylated Src (p-Src), and p-Stat3 were increased in A431-III cells. Flavonoids Lu and Qu reduce protein levels of p-Src, p-Stat3 and S100A7 in A431-III cells. Treatment of A431-III cells with Src inhibitor SU6656 and Stat3 inhibitor S3I-201 also reduced the protein levels of S100A7. Transactivation activity of 5&prime upstream regions of S100A7 was activated by Stat3 but was reduced by treatment with Lu, Qu, SU6656 and S3I-201. The treatment also reduced the migratory and invasive abilities of A431-III cells. In a further analysis of EMT markers, the protein level of E-cad increased and that of Twist decreased after treatment with the inhibitors and flavonoids. Overexpression of S100A7 decreased the protein level of E-cad and increased the Twist level, whereas knockdown of S100A7 had the opposite effects. Treatment with S3I-201, Lu and Qu, compared to the control, were found to decrease metastasis of tumor cells in zebrafish larvae. These results suggest that Lu and Qu may inhibit Src/Stat3/S100A7 signaling to reduce tumorigenesis of cancer cells. |
| Databáze: | OpenAIRE |
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