title: LW-213 induces G2/M cell cycle arrest through AKT/GSK3β/β-catenin signaling pathway in human breast cancer cells.
abstract: LW-213 is a derivative of Wogonin and the anticancer activities of Wogonin have been reported. To study whether LW-213 inhibits cancer cells and explore a possible mechanism, we investigate the compound in several cancer cell lines. We found LW-213 arrests G2/M cycle in breast cancer cells by suppression of Akt/Gsk3β/β-catenin signaling pathway. In compound treated cells, cell cycle-related proteins cyclin A, cyclin B1, p-CDK1, p-Cdc25C, and p-Chk2 (Thr68) were upregulated, and β-catenin nuclear translocation was inhibited. Electrophoretic mobility shift assay revealed LW-213 inhibits binding of β-catenin/LEF complex to DNA. GSK3β inhibitor LiCl and siRNA against GSK3β partially reversed G2/M arrest in breast cancer MCF-7 cells. These results suggest LW-213 triggered G2/M cell cycle arrest through suppression of β-catenin signaling. In BALB/c mice, growth of xenotransplanted MCF-7 tumor was also inhibited after treatment of LW-213. Regulation of cyclin A, cyclin B1, and β-catenin by LW-213 in vivo was the same as in vitro study. In conclusion, we found LW-213 exerts its anticancer effect on cell proliferation and cell cycle through repression of Akt/Gsk3β/β-catenin signaling pathway. LW-213 could be a potential candidate for anticancer drug development.
authors.affiliation: School of pharmacy, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of pharmacy, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Han-Chi
authors.initials: HC
authors.lastname: Miao
authors.affiliation: School of pharmacy, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Li
authors.affiliation: School of pharmacy, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of pharmacy, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Shao-Liang
authors.initials: SL
authors.lastname: Huang
authors.affiliation: School of pharmacy, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Li
authors.affiliation: School of pharmacy, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D044950:Flavanones / Q000008:administration & dosage* / Q000494:pharmacology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D061986:MCF-7 Cells; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride; C085514:wogonin
keywords: Akt/Gsk3β/β-catenin signaling pathway; G2/M arrest; LW-213; Wogonin derivative; breast cancer