title: 8-Bromo-7-methoxychrysin-blocked STAT3/Twist axis inhibits the stemness of cancer stem cell-like cell originated from SMMC-7721 cells.
abstract: Signal transducer and activator of transcription 3 (STAT3) is a member of the family of latent cytoplasmic transcriptional factors that could regulate cell proliferation, survival, and development. It has been reported that Twist is a target gene of STAT3, and STAT3/Twist signaling plays an important role in regulating cancer progress. Here, to explore whether 8-bromo-7-methoxychrysin (BrMC) inhibits liver cancer stem-like cell (LCSLC) properties via disrupting STAT3/Twist signaling, we cultured SMMC-7721 cells in vitro, and evaluated the effects of BrMC on the stemness of spheroids by determining the sphere-forming capability and migration. The sphere formation assay results showed a concentration-dependent decrease of sphere-forming capacity in LCSLCs (P < 0.05) treated with different concentrations of BrMC. Wound-healing assays results demonstrated a concentration-dependent decline in cell migration of LCSLCs treated with different concentrations of BrMC. In addition, CD133, CD44, and ALDH1 levels were decreased in LCSLCs treated with BrMC. Treatment with different concentrations of BrMC also reduced the expressions of p-STAT3 and Twist1 proteins. The effect of BrMC was substantially enhanced by co-treatment with JSI-124, a specific inhibitor of STAT3. Ectopic expression of Twist1 attenuated the inhibitory effects of BrMC on sphere formation, migration, and expression of the markers in LCSLCs. However, it had no affect on p-STAT3 expression in LCSLCs. These results demonstrated that BrMC inhibits the stemness of LCSLCs originated from SMMC-7721 cell line by inhibiting STAT3/Twist signal axis.
authors.affiliation: Cancer Institute, Medical College, University of South China, Hengyang 421001, China.|Key Laboratory of Tumor Cellular & Molecular Pathology, University of South China, engyang 421001, China.|Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha410013, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Laboratory of Molecular and Statistical Genetics, Hunan Normal University, Changsha 410081, China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha410013, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha410013, China.
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha410013, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular and Statistical Genetics, Hunan Normal University, Changsha 410081, China.
authors.forename: Xiangding
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha410013, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*
chemical_list: C552860:8-bromo-7-methoxychrysin; D000970:Antineoplastic Agents; D005419:Flavonoids; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051879:Twist-Related Protein 1
keywords: 8-bromo-7-methoxychysin; STAT3; Twist; cancer stem cell; liver cell carcinoma