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Abstract Title:

Chrysin Inhibits Proinflammatory Factor-Induced EMT Phenotype and Cancer Stem Cell-Like Features in HeLa Cells by Blocking the NF-κB/Twist Axis.

Abstract Source:

Cell Physiol Biochem. 2019 ;52(5):1236-1250. PMID: 31001962

Abstract Author(s):

Weilei Dong, A Chen, Xiaocheng Chao, Xiang Li, YingHong Cui, Chang Xu, Jianguo Cao, Yingxia Ning

Article Affiliation:

Weilei Dong

Abstract:

BACKGROUND/AIMS: TNF-α and TGF-β associated epithelial-mesenchymal transition (EMT) occurs via NF-κB-dependent transcriptional upregulation of Twist1.Chrysin (ChR) is a major active ingredient ofpropolis, which inhibits various cancer cells and possesses anti-inflammatory activities. This study aimed to assess whether and how ChR inhibits proinflammatory cytokine-induced EMT phenotype and cancer stem-like cell (CSLC) features in the HeLa cell line.

METHODS: HeLa cells were co-administered TNF-α (10.0 ng/mL) and TGF-β (5.0 ng/mL) for 24h following TGF-β (5.0 ng/mL) alone for 6 d in the presence or absence of ChR (5.0, 10.0 and 20.0μM). Then, the levels of EMT-related factors, multi-potential transcription factors, and stem cell markers were analyzed by immunoblot. Wound healing and tumor sphere formation assays were performed to assess the migration and self-renewal capabilities of cells, respectively. Overexpression and/or knockdown of NF-κBp65 and/or Twsit1 were used to explore the molecular mechanisms.

RESULTS: The results showed that ChR inhibited EMT and CSLC properties in HeLa cells administered TNF-α after prolonged TGF-β treatment, in a concentration-dependent fashion. NF-κBp65 knockdown and ChR(10.0μM) cooperatively enhanced the inhibition of NF-κBp65 and Twist1 expression, EMT, and CSLC properties. Conversely, overexpression of NF-κBp65 combined with ChR(10.0μM) antagonized such activities. Meanwhile, Twist1silencing or overexpression combined with ChR treatment did not affect NF-κBp65 levels, but also reduced or enhanced EMT and CSLC properties. Importantly, overexpressing Twist1 combined with ChR reversed the effects of NF-κBp65 knockdown and ChR.

CONCLUSION: ChR inhibits proinflammatory cytokine-induced EMT and CSLC features in HeLa cells by blocking the NF-κB/Twist axis.

Study Type : In Vitro Study

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Sayer Ji
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