title: Ursolic acid inhibits the growth of colon cancer-initiating cells by targeting STAT3.
abstract: BACKGROUND
  We have previously reported Signal Transducer and Activator of Transcription 3 (STAT3) to be constitutively activated in aldehyde dehydrogenase (ALDH)(+)/cluster of differentiation-133 (CD133)(+) colon cancer-initiating cells. In the present study we tested the efficacy of inhibiting STAT3 signaling in human colon cancer-initiating cells by ursolic acid (UA), which exists widely in fruits and herbs.
  
  
  RESULTS
  Our data demonstrated that UA inhibited STAT3 phosphorylation, and induced caspase-3 cleavage of ALDH(+)/CD133(+) colon cancer-initiating cells. UA also reduced cell viability and inhibited tumor sphere formation of colon cancer-initiating cells, more potently than two other natural compounds, resveratrol and capsaicin. UA also inhibited the activation of STAT3 induced by interleukin-6 in DLD-1 colon cancer cells. Furthermore, daily administration of UA suppressed HCT116 tumor growth in mice in vivo.
  
  
  CONCLUSIONS
  Our results suggest STAT3 to be a target for colon cancer prevention. UA, a dietary agent, might offer an effective approach for colorectal carcinoma prevention by inhibiting persistently activated STAT3 in cancer stem cells.
authors.affiliation: Department of Pediatrics, College of Medicine, The Ohio State University, 700 Children's Drive, Columbus, OH 43205, U.S.A. Tel: +1 6147225086, lin.674@osu.edu.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Wang
authors.forename: Chongqiang
authors.initials: C
authors.lastname: Zhao
authors.forename: David
authors.initials: D
authors.lastname: Jou
authors.forename: Jiagao
authors.initials: J
authors.lastname: Lü
authors.forename: Cuntai
authors.initials: C
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D000097245:Ursolic Acid; C494086:STAT3 protein, human; C505407:CASP3 protein, human
keywords: STAT3; Ursolic acid; cancer-initiating cells; colon cancer