Dietary flavonoids, luteolin and quercetin, inhibit invasion of cervical cancer by reduction of UBE2S through epithelial–mesenchymal transition signaling
| Autor: | Cheng Wei Lin, Tsung Han Lin, Ming Ting Lee, Geen-Dong Chang, Wen Hsien Hsu, Pei Hsun Tsai, Chithan C. Kandaswami, Ku Chung Chen, Ying Tang Huang, Inn Ho Tsai, Chia Hsiung Cheng, Chang Jen Huang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Uterine Cervical Neoplasms Motility 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ubiquitin Cell Line Tumor Humans Neoplasm Invasiveness heterocyclic compounds Epithelial–mesenchymal transition Luteolin Gene knockdown biology General Medicine 030104 developmental biology chemistry Biochemistry Cell culture 030220 oncology & carcinogenesis Dietary Supplements Ubiquitin-Conjugating Enzymes Cancer cell biology.protein Cancer research Female Quercetin Signal Transduction Food Science |
| Zdroj: | Food & Function. 8:1558-1568 |
| ISSN: | 2042-650X 2042-6496 |
| Popis: | We previously reported that the dietary flavonoids, luteolin and quercetin, might inhibit the invasiveness of cervical cancer by reversing epithelial-mesenchymal transition (EMT) signaling. However, the regulatory mechanism exerted by luteolin and quercetin is still unclear. This study analyzed the invasiveness activation by ubiquitin E2S ligase (UBE2S) through EMT signaling and inhibition by luteolin and quercetin. We found that UBE2S expression was significantly higher in highly invasive A431 subgroup III (A431-III) than A431-parental (A431-P) cells. UBE2S small interfering (si)RNA knockdown and overexpression experiments showed that UBE2S increased the migratory and invasive abilities of cancer cells through EMT signaling. Luteolin and quercetin significantly inhibited UBE2S expression. UBE2S showed a negative correlation with von Hippel-Lindau (VHL) and a positive correlation with hypoxia-induced factor (Hif)-1α. Our findings suggest that high UBE2S in malignant cancers contributes to cell motility through EMT signaling and is reversed by luteolin and quercetin. UBE2S might contribute to Hif-1α signaling in cervical cancer. These results show the metastatic inhibition of cervical cancer by luteolin and quercetin through reducing UBE2S expression, and provide a functional role for UBE2S in the motility of cervical cancer. UBE2S could be a potential therapeutic target in cervical cancer. |
| Databáze: | OpenAIRE |
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