title: U12, a UDCA derivative, acts as an anti-hepatoma drug lead and inhibits the mTOR/S6K1 and cyclin/CDK complex pathways.
abstract: U12, one of 20 derivatives synthesized from ursodeoxycholic acid (UDCA), has been found to have anticancer effects in liver cancer cell lines (SMMC-7721 and HepG2) and to protect normal liver cells from deoxycholic acid (DCA) damage (QSG-7701). Its anticancer mechanism was investigated using computer-aided network pharmacology and comparative proteomics. Results showed that its anti-malignancy activities were activated by mTOR/S6K1, cyclinD1/CDK2/4 and caspase-dependent apoptotic signaling pathways in hepatocellular carcinoma cells (HCC). The action of U12 may be similar to that of rapamycin. Animal testing confirmed that U12 exerted better anti-tumor activity than UDCA and had less severe side effects than fluorouracil (5-Fu). These observations indicate that U12 differs from UDCA and other derivatives and may be a suitable lead for the development of compounds useful in the treatment of HCC.
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Luo
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Dequan
authors.initials: D
authors.lastname: Zeng
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ding
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China; Sanford-Burnham Medical Research Institute, La Jolla, California, United States of America.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D011485:Protein Binding; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016213:Cyclins; D014580:Ursodeoxycholic Acid; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D018844:Cyclin-Dependent Kinases