6,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signaling

The hepatic metabolites of daidzein has been demonstrated to be more potent in chronic diseases than daidzein. However, the investigation of their roles in estrogen receptor (ER)-negative breast cancer is limited. Here, the hepatic metabolite of daidzein 6,7,4′-trihydroxyisoflavone inhibited cell pr...

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Main Authors: Jing Chen, Jaehoo Lee, Cheng Bao, Jin Tae Kim, Hong Jin Lee
Format: Article
Language:English
Published: Elsevier 2018-09-01
Series:Journal of Functional Foods
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1756464618303797
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author Jing Chen
Jaehoo Lee
Cheng Bao
Jin Tae Kim
Hong Jin Lee
author_facet Jing Chen
Jaehoo Lee
Cheng Bao
Jin Tae Kim
Hong Jin Lee
author_sort Jing Chen
collection DOAJ
description The hepatic metabolites of daidzein has been demonstrated to be more potent in chronic diseases than daidzein. However, the investigation of their roles in estrogen receptor (ER)-negative breast cancer is limited. Here, the hepatic metabolite of daidzein 6,7,4′-trihydroxyisoflavone inhibited cell proliferation, induced cell cycle arrest at G2/M phase, and regulated the expression of cyclin B, cyclin dependent kinase (CDK)-1 and CDK2 in MCF10DCIS.com ER-negative breast cancer cells. 6,7,4′-Trihydroxyisoflavone activated glycogen synthase kinase (GSK)-3β, and suppressed the nuclear translocation of β-catenin. Inhibition of GSK3β by lithium chloride reversed the effect of 6,7,4′-trihydroxyisoflavone on β-catenin localization, CDK1, CDK2 and cyclin B expression, and the proliferation of MCF10DCIS.com. In xenograft animal model, 6,7,4′-trihydroxyisoflavone inhibited tumor growth, and regulated GSK3β phosphorylation and β-catenin nuclear localization. These results indicate that 6,7,4′-trihydroxyisoflavone suppressed ER-negative breast cancer growth through regulating GSK3β/β-catenin signaling, and 6,7,4′-trihydroxyisoflavone may be a potent chemopreventive agent in regulating the ER-negative human mammary carcinogenesis.
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spelling doaj.art-38f6b3bc953f47ccafaf6a35bcb979372022-12-21T23:22:19ZengElsevierJournal of Functional Foods1756-46462018-09-01484985066,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signalingJing Chen0Jaehoo Lee1Cheng Bao2Jin Tae Kim3Hong Jin Lee4Department of Food Science and Technology, Chung-Ang University, Anseong 17546, South KoreaDepartment of Food Science and Technology, Chung-Ang University, Anseong 17546, South KoreaDepartment of Food Science and Technology, Chung-Ang University, Anseong 17546, South KoreaDepartment of Food Science and Technology, Chung-Ang University, Anseong 17546, South KoreaCorresponding author.; Department of Food Science and Technology, Chung-Ang University, Anseong 17546, South KoreaThe hepatic metabolites of daidzein has been demonstrated to be more potent in chronic diseases than daidzein. However, the investigation of their roles in estrogen receptor (ER)-negative breast cancer is limited. Here, the hepatic metabolite of daidzein 6,7,4′-trihydroxyisoflavone inhibited cell proliferation, induced cell cycle arrest at G2/M phase, and regulated the expression of cyclin B, cyclin dependent kinase (CDK)-1 and CDK2 in MCF10DCIS.com ER-negative breast cancer cells. 6,7,4′-Trihydroxyisoflavone activated glycogen synthase kinase (GSK)-3β, and suppressed the nuclear translocation of β-catenin. Inhibition of GSK3β by lithium chloride reversed the effect of 6,7,4′-trihydroxyisoflavone on β-catenin localization, CDK1, CDK2 and cyclin B expression, and the proliferation of MCF10DCIS.com. In xenograft animal model, 6,7,4′-trihydroxyisoflavone inhibited tumor growth, and regulated GSK3β phosphorylation and β-catenin nuclear localization. These results indicate that 6,7,4′-trihydroxyisoflavone suppressed ER-negative breast cancer growth through regulating GSK3β/β-catenin signaling, and 6,7,4′-trihydroxyisoflavone may be a potent chemopreventive agent in regulating the ER-negative human mammary carcinogenesis.http://www.sciencedirect.com/science/article/pii/S1756464618303797Breast cancerβ-cateninCell cycleGlycogen synthase kinase-3βTrihydroxyisoflaovone
spellingShingle Jing Chen
Jaehoo Lee
Cheng Bao
Jin Tae Kim
Hong Jin Lee
6,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signaling
Journal of Functional Foods
Breast cancer
β-catenin
Cell cycle
Glycogen synthase kinase-3β
Trihydroxyisoflaovone
title 6,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signaling
title_full 6,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signaling
title_fullStr 6,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signaling
title_full_unstemmed 6,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signaling
title_short 6,7,4′-Trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase-3β/β-catenin signaling
title_sort 6 7 4 trihydroxyisoflavone suppressed the estrogen receptor negative breast cancer growth via regulating glycogen synthase kinase 3β β catenin signaling
topic Breast cancer
β-catenin
Cell cycle
Glycogen synthase kinase-3β
Trihydroxyisoflaovone
url http://www.sciencedirect.com/science/article/pii/S1756464618303797
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