PMID- 31933724 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200117 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 12 IP - 1 DP - 2019 TI - NF-kappaB/Twist axis is involved in chysin inhibition of ovarian cancer stem cell features induced by co-treatment of TNF-alpha and TGF-beta. PG - 101-112 AB - Chrysin (ChR) inhibits various cancer cells and possesses anti-inflammatory activities. NF-kB has been shown to regulate the expression of genes involved in epithelial-mesenchymal transformation (EMT) by upregulation of TWIST1. This study aimed to assess whether ChR can inhibit EMT phenotype and cancer stem-like cell (CSLC) features in ovarian cancer cells co-treated with TNF-alpha and TGF-beta. Here, OVCAR-3 cells were co-treated with TNF-alpha and TGF-beta in the presence or absence of ChR. Then, the expression levels of E-cadherin, N-cadherin, CD133, CD44, NF-kappaBp65, and TWIST1 were analyzed by western blotting. Wound healing and tumor sphere formation assays were performed to assess the migration and sphere-forming capabilities of cells, respectively. Overexpression and/or knockdown of NF-kappaBp65 and/or TWIST1 were used to explore the molecular mechanisms. We showed that ChR inhibited EMT and CSLC properties in ovarian cancer cells administered TNF-alpha after prolonged TGF-beta treatment, in a dose-dependent manner. Also, knockdown of NF-kappaBp65 and ChR cooperatively enhanced the inhibition of NF-kappaBp65 and TWIST1 expression, EMT phenotype, and CSLC properties. Conversely, overexpression of NF-kappaBp65 antagonized the above-mentioned activities of ChR. Furthermore, TWIST1 silencing or overexpression did not affect the ChR treatment effect on NF-kappaBp65 levels, but it reduced or enhanced EMT and CSLC properties. In conclusion, ChR can inhibit a proinflammatory cytokine to induce EMT and CSLC characteristics in OVCAR-3 cells, which may be involved in blocking the NF-kappaB/Twist axis. CI - IJCEP Copyright (c) 2019. FAU - Li, Huazhen AU - Li H AD - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University 511447, Guangdong, China. FAU - Chen, A AU - Chen A AD - Department of Pharmaceutical Science, Medical College, Hunan Normal University, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province Changsha 410013, China. FAU - Yuan, Qiaoqi AU - Yuan Q AD - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University 511447, Guangdong, China. FAU - Chen, Weifeng AU - Chen W AD - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University 511447, Guangdong, China. FAU - Zhong, Huimin AU - Zhong H AD - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University 511447, Guangdong, China. FAU - Teng, Mo AU - Teng M AD - Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Guangzhou Medical University 511447, Guangdong, China. FAU - Xu, Chang AU - Xu C AD - Department of Pharmaceutical Science, Medical College, Hunan Normal University, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province Changsha 410013, China. FAU - Qiu, Yebei AU - Qiu Y AD - Department of Pharmaceutical Science, Medical College, Hunan Normal University, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province Changsha 410013, China. FAU - Cao, Jianguo AU - Cao J AD - Department of Pharmaceutical Science, Medical College, Hunan Normal University, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province Changsha 410013, China. LA - eng PT - Journal Article DEP - 20190101 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 PMC - PMC6943996 OTO - NOTNLM OT - NF-kappaB OT - Ovarian cancer OT - TWIST1 OT - cancer stem cells OT - chrysin OT - epithelial-mesenchymal transition COIS- None. EDAT- 2020/01/15 06:00 MHDA- 2020/01/15 06:01 PMCR- 2019/01/01 CRDT- 2020/01/15 06:00 PHST- 2018/09/08 00:00 [received] PHST- 2018/11/06 00:00 [accepted] PHST- 2020/01/15 06:00 [entrez] PHST- 2020/01/15 06:00 [pubmed] PHST- 2020/01/15 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] PST - epublish SO - Int J Clin Exp Pathol. 2019 Jan 1;12(1):101-112. eCollection 2019.