title: Dietary flavonoids, luteolin and quercetin, inhibit invasion of cervical cancer by reduction of UBE2S through epithelial-mesenchymal transition signaling.
abstract: 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.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.
authors.forename: Tsung-Han
authors.initials: TH
authors.lastname: Lin
authors.forename: Wen-Hsien
authors.initials: WH
authors.lastname: Hsu
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Tsai
authors.forename: Ying-Tang
authors.initials: YT
authors.lastname: Huang
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Lin
authors.forename: Ku-Chung
authors.initials: KC
authors.lastname: Chen
authors.forename: Inn-Ho
authors.initials: IH
authors.lastname: Tsai
authors.forename: Chithan C
authors.initials: CC
authors.lastname: Kandaswami
authors.forename: Chang-Jen
authors.initials: CJ
authors.lastname: Huang
authors.forename: Geen-Dong
authors.initials: GD
authors.lastname: Chang
authors.forename: Ming-Ting
authors.initials: MT
authors.lastname: Lee
authors.forename: Chia-Hsiung
authors.initials: CH
authors.lastname: Cheng
mesh_terms: D045744:Cell Line, Tumor; D019587:Dietary Supplements / Q000032:analysis; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D011794:Quercetin; C544962:Ube2S protein, human; D044763:Ubiquitin-Conjugating Enzymes; D047311:Luteolin