title: Flavone inhibits migration through DLC1/RhoA pathway by decreasing ROS generation in breast cancer cells.
abstract: Tumor suppressor protein deleted in liver cancer 1 (DLC1) is a RhoGTPase-activating protein (RhoGAP) and inhibits cancer cell migration by inactivating downstream target protein RhoA. A few studies have reported the regulations of reactive oxygen species (ROS) on RhoGAP. In this study, we investigated flavone (the core structure of flavonoids)-induced regulation on ROS generation and DLC1/RhoA pathway in MCF-7 and MDA-MB-231 breast cancer cells and explored whether flavone-induced upregulation of DLC1 is mediated by ROS. Our results showed that flavone decreased ROS production and inhibited cell migration through DLC1/RhoA pathway. To further investigate the role of ROS in flavone-induced regulation on DLC1/RhoA pathway, hydrogen peroxide was added to restore the ROS levels. Flavone-induced upregulation of DLC1 expression, downregulation of RhoA activity, and inhibition of cell migration were all restrained by hydrogen peroxide. We also found that flavone increased DLC1 stability by inhibiting DLC1 protein degradation in breast cancer cells. In summary, our study demonstrated that flavone inhibited cell migration through DLC1/RhoA pathway by decreasing ROS generation and suppressed DLC1 degradation in MCF-7 and MDA-MB-231 breast cancer cells.
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Bingwu
authors.initials: B
authors.lastname: Yang
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Zhaodi
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Rongfei
authors.initials: R
authors.lastname: Chai
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Taiyu
authors.initials: T
authors.lastname: Song
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Li
authors.affiliation: Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan, 250014, China. grli@sdnu.edu.cn.
authors.forename: Guorong
authors.initials: G
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D047309:Flavones / Q000494:pharmacology*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C112352:DLC1 protein, human; D047309:Flavones; D020690:GTPase-Activating Proteins; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; D020742:rhoA GTP-Binding Protein; C043562:flavone
keywords: Breast cancer cells; DLC1/RhoA pathway; Flavone; Migration; ROS