title: Curcumin-cyclodextrin complexes potentiate gemcitabine effects in an orthotopic mouse model of lung cancer.
abstract: BACKGROUND
  Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer.
  
  
  METHODS
  Owing to poor curcumin solubility, we have used cyclodextrins (CD) as an excipient allowing a considerable increase of aqueous solubility and bioavailability of curcumin. The effects of solubilised curcumin have been evaluated in cell cultures as well as in an in vivo orthotopic lung tumour mouse model.
  
  
  RESULTS
  Cell proliferation was reduced while apoptosis rates were increased when lung epithelial tumour cells were cultured in the presence of curcumin-CD complexes. For in vivo experiments, cells were grafted into lungs of C57Bl/6 mice treated by an oral administration of a non-soluble form of curcumin, CDs alone or curcumin-CD complexes, combined or not with gemcitabine. The size of orthotopically implanted lung tumours was reduced upon curcumin complex administration as compared with treatments with placebo or non-solubilised curcumin. Moreover, curcumin potentiated the gemcitabine-mediated antitumour effects.
  
  
  CONCLUSIONS
  Our data demonstrate that curcumin, when given orally in a CD-solubilised form, reduces lung tumour size in vivo. In vitro experiments show impaired tumour cell proliferation and increased cell apoptosis. Moreover, our data underline a potential additive effect of curcumin with gemcitabine thus providing an efficient therapeutic option for antilung cancer therapy.
authors.affiliation: Laboratory of Tumor and Development Biology, GIGA-Research (Groupe Interdisciplinaire de Génoprotéomique Appliquée) - GIGA-Cancer and GIGA-I, University of Liege and CHU of Liege, Sart-Tilman, 4000 Liege, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Rocks
authors.forename: S
authors.initials: S
authors.lastname: Bekaert
authors.forename: I
authors.initials: I
authors.lastname: Coia
authors.forename: G
authors.initials: G
authors.lastname: Paulissen
authors.forename: M
authors.initials: M
authors.lastname: Gueders
authors.forename: B
authors.initials: B
authors.lastname: Evrard
authors.forename: J-C
authors.initials: JC
authors.lastname: Van Heugen
authors.forename: P
authors.initials: P
authors.lastname: Chiap
authors.forename: J-M
authors.initials: JM
authors.lastname: Foidart
authors.forename: A
authors.initials: A
authors.lastname: Noel
authors.forename: D
authors.initials: D
authors.lastname: Cataldo
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004357:Drug Synergism; D016195:G2 Phase / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D003505:Cyclodextrins; D003841:Deoxycytidine; D003474:Curcumin; D000093542:Gemcitabine