LW‐213 induces G2/M cell cycle arrest through AKT/GSK3β/β‐catenin signaling pathway in human breast cancer cells. Issue 5 (6th May 2015)

• Record Type: Journal Article
• Authors: Zhao, Li; Miao, Han‐Chi; Li, Wen‐Jun; Sun, Yang; Huang, Shao‐liang; Li, Zhi‐Yu; Guo, Qing‐Long
• Is Part Of: Molecular carcinogenesis. Volume 55:Issue 5(2016:May)
• Page Start: 778
• Page End: 792
• Publication Date: 2015-05-06
• Subjects: LW‐213 -- Wogonin derivative -- G2/M arrest -- Akt/Gsk3β/β‐catenin signaling pathway -- breast cancer; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22321
• Languages: English
• ISSNs: 0899-1987

Abstract

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. © 2015 Wiley Periodicals, Inc.