title: Role of ursolic acid chalcone, a synthetic analogue of ursolic acid, in inhibiting the properties of CD133(+) sphere-forming cells in liver stem cells.
abstract: The expression of CD133 decreases with differentiation of tumor cell, indicating that CD133 is a specific marker for isolation and identification of CSCs. In the present study the effect of Ursolic acid chalcone (UAC) on CD133(+) hepatocellular carcinoma cell (HCC CSCs) differentiation, their self-renewal, tumorigenic capacity and sensitivity to chemotherapeutic drugs was studied. The results demonstrated that UAC inhibits the expression of CD133(+) in a dose and time-dependent manner in PLC/PRF/5 and Huh7 HCC cells. The inhibition was significant at 50 μM and on day 8. The percentage of CD133(+) cells decreased from an initial 59.3% in PLC/PRF/5 to 37.1% and 78.2% in Huh7 to 59.2% on treatment with UAC. There was inhibition of Oct4, Tert, Bmi1, β-catenin, ABCG2, and tumor sphere-related gene Ep300. In addition it also decreased number of CK19-positive cells and increased number of CK8/18-positive cells. UAC treatment caused a decrease in self-renewal capability and increase in sensitivity to doxorubicin and vincristine drugs in CD133(+) HCC CSCs. Therefore, UAC can be a potent therapeutic agent to target differentiation of CSC in HCC.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, The Second Hospital of Jilin University Changchun 130041, China.
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Lin
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, The Second Hospital of Jilin University Changchun 130041, China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Gong
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University Changchun 130041, China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Fan
authors.affiliation: Department of Medicine, Jilin University Changchun 130041, China.
authors.forename: Zhong-Kai
authors.initials: ZK
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, The Second Hospital of Jilin University Changchun 130041, China.
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Yang
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D002599:Chalcone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010455:Peptides / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D002599:Chalcone; D006023:Glycoproteins; D010455:Peptides; D014315:Triterpenes; D000097245:Ursolic Acid; C000606023:PROM1 protein, human
keywords: Self-renewal; cell differentiation; hepatocellular carcinoma; therapeutic agent