title: Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030.
abstract: BACKGROUND
  Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer, including colon cancer. To date, whether STAT3 is activated and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, in colon cancer stem cells are still unknown.
  
  
  METHODS
  Flow cytometry was used to isolate colon cancer stem cells, which are characterised by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulations (ALDH(+)/CD133(+)). The levels of STAT3 phosphorylation and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, that targets STAT3 in colon cancer stem cells were examined.
  
  
  RESULTS
  Our results observed that ALDH(+)/CD133(+) colon cancer cells expressed higher levels of phosphorylated STAT3 than ALDH-negative/CD133-negative colon cancer cells, suggesting that STAT3 is activated in colon cancer stem cells. GO-Y030 and curcumin inhibited STAT3 phosphorylation, cell viability, tumoursphere formation in colon cancer stem cells. GO-Y030 also reduced STAT3 downstream target gene expression and induced apoptosis in colon cancer stem cells. Furthermore, GO-Y030 suppressed tumour growth of cancer stem cells from both SW480 and HCT-116 colon cancer cell lines in the mouse model.
  
  
  CONCLUSIONS
  Our results indicate that STAT3 is a novel therapeutic target in colon cancer stem cells, and inhibition of activated STAT3 in cancer stem cells by GO-Y030 may offer an effective treatment for colorectal cancer.
authors.affiliation: Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205, USA. lin.674@osu.edu
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: P-K
authors.initials: PK
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Fuchs
authors.forename: H
authors.initials: H
authors.lastname: Shibata
authors.forename: Y
authors.initials: Y
authors.lastname: Iwabuchi
authors.forename: J
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007659:Ketones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C541015:1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one; D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D007659:Ketones; D003474:Curcumin