title: CWP232228 targets liver cancer stem cells through Wnt/β-catenin signaling: a novel therapeutic approach for liver cancer treatment.
abstract: Liver cancer stem cells (CSCs) are resistant to conventional chemotherapy and radiation, which may destroy tumor masses, but not all liver CSCs contribute to tumor initiation, metastasis, and relapse. In the present study, we showed that liver CSCs with elevated Wnt/β-catenin signaling possess much greater self-renewal and clonogenic potential. We further documented that the increased clonogenic potential of liver CSCs is highly associated with changes in Wnt/β-catenin signaling and that Wnt/β-catenin signaling activity is positively correlated with CD133 expression and aldehyde dehydrogenase (ALDH) enzymatic activity. Notably, the small molecule inhibitor CWP232228, which antagonizes the binding of β-catenin to TCF in the nucleus, inhibits Wnt/β-catenin signaling and depletes CD133+/ALDH+ liver CSCs, thus ultimately diminishing the self-renewal capacity of CSCs and decreasing tumorigenicity in vitro and in vivo. Taken together, our findings suggest that CWP232228 acts as a candidate therapeutic agent for liver cancer by preferentially targeting liver CSCs.
authors.affiliation: Center of Animal Care and Use, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.|Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: The Faculty of Liberal Arts, Jungwon University, Chungbuk, Republic of Korea.
authors.forename: Hwa-Yong
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, Catholic University of Daegu, Daegu, Republic of Korea.
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.affiliation: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Yang-Kyu
authors.initials: YK
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Nam
authors.affiliation: Laboratory of Stem Cell Research, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Republic of Korea.|Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Republic of Korea.
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010755:Organophosphates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D053961:Azabicyclo Compounds; D014408:Biomarkers, Tumor; C000600091:CWP232228; D010755:Organophosphates; D051153:Wnt Proteins; D051176:beta Catenin
keywords: ALDH; CD133; CWP232228; Wnt/β-catenin signaling; cancer stem cells