Abstract 4228: 6,7,4-Trihydroxyisoflavone, a daidzein metabolites, regulated glycogen synthase kinase 3β/β-catenin signaling and inhibited cell proliferation in MCF10DCIS.com human breast cancer cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.4228-4228
• Main Authors: Park, Hyun-Chang, Bao, Cheng, Ko, Jiwon, Lee, Jaehoo, Lee, Hong Jin
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-4228

Recent studies have demonstrated that hepatic daidzein metabolites exerted significant activities in regulating different types of cancer including skin and colon. However, the role of daidzein metabolites on breast cancer has not been extensively studied. In this study, we found that 6,7,4′-trihydroxyisoflavone exerted the strongest inhibitory effect on the proliferation of MCF10DCIS.com human breast cancer cells among the daidzein metabolites we tested. Cell cycle at S and G2/M phase were arrested by 6,7,4-trihydroxyisoflavone, which were derived from regulating cyclins and cyclin dependent kinases (CDKs) including cyclin B, CDK1 and CDK2, as well as CDK inhibitor, p27 in a dose dependent manner. Furthermore, 6,7,4′-trihydroxyisoflavone increased the GSK3β activity through inhibiting the phosphorylation at Ser9, which was caused by the enhancement of phosphatase activity. These effects of 6,7,4′-trihydroxyisoflavone led to inhibition of the nuclear translocation of β-catenin, and regulation of cell cycle related proteins, cyclinB and CDK2. Taken together, 6,7,4′-trihydroxyisoflavone regulated GSK3β/β-catenin signaling, and arrested at S and G2/M phase in MCF10DCIS.com human breast cancer cells, and it suggests that the hepatic metabolite of daidzein, 6,7,4′-trihydroxyisoflavone, may be a potent agent in inhibiting MCF10DCIS.com human breast cancer growth. Citation Format: Hyun-Chang Park, Cheng Bao, Jiwon Ko, Jaehoo Lee, Hong Jin Lee. 6,7,4-Trihydroxyisoflavone, a daidzein metabolites, regulated glycogen synthase kinase 3β/β-catenin signaling and inhibited cell proliferation in MCF10DCIS.com human breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4228. doi:10.1158/1538-7445.AM2014-4228