title: Coadministration of a Gloriosa superba extract improves the in vivo antitumoural activity of gemcitabine in a murine pancreatic tumour model.
abstract: BACKGROUND
  Gloriosa superba L. (glory lily, Colchicaceae) contains colchicine, and related alkaloids such as 3-O-demethylcolchicine and its glycoside colchicoside. Previously the in vivo efficacy of a crude extract and a colchicine-poor / colchicoside-rich extract of G. superba seeds was shown in a murine model of pancreatic adenocarcinoma.
  
  
  OBJECTIVE
  The efficacy can be improved without obvious signs of toxicity by increasing the treatment dose; the efficacy of gemcitabine can be improved by coadministration of a Gloriosa superba extract.
  
  
  METHODS
  A survival experiment was carried out in a murine model of pancreatic adenocarcinoma and the semi-long-term toxicity of both G. superba extracts was determined; a combination therapy with gemcitabine was evaluated.
  
  
  METHODS
  A crude ethanolic extract (GS) and a colchicine-poor / colchicoside-rich extract (GS2B) were prepared, containing 3.22% colchicine, 2.52% colchicoside and 1.52% 3-O-demethylcolchicine (GS), and 0.07%, 2.26% and 0.46% (m/m) (GS2B). They were evaluated in a murine model of pancreatic adenocarcinoma at a dose of 4.5mg/kg (p.o., daily) total content of colchicine and derivatives during 3 weeks, or at 3.0mg/kg (p.o., daily) combined with gemcitabine (60mg/kg, i.p., 3x/week) during 54 days.
  
  
  RESULTS
  A significant effect in tumour growth over time was observed for gemcitabine and the combination therapy compared to the control group. No significant difference was observed for the groups treated with colchicine and both extracts. However, combination therapy was significantly better than the monotherapy with gemcitabine. Moreover, survival analysis showed a significant prolongation of the survival of the groups treated with gemcitabine and the combination therapy. A slight difference in survival was observed between gemcitabine and the combination therapy, the latter one being slightly better. No significant prolongation of survival was observed for the extracts and colchicine compared to the control group.
  
  
  CONCLUSIONS
  Although a relevant tumour growth inhibition and a difference of relative tumour volume compared to the control group were observed on day 11, and a slightly longer survival was noticed for GS2B, the most important conclusion from this study is that the crude G. superba extract (GS) might have an added value combined with gemcitabine in the treatment of pancreatic tumours.
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp (Wilrijk), Belgium.
authors.forename: Rica
authors.initials: R
authors.lastname: Capistrano I
authors.affiliation: Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium; Molecular Imaging Center Antwerp (MICA), University of Antwerp, Antwerp (Wilrijk), Belgium.
authors.forename: Christel
authors.initials: C
authors.lastname: Vangestel
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp (Wilrijk), Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vanpachtenbeke
authors.affiliation: StatUa Center for Statistics, University of Antwerp, Prinsstraat 13, 2000 Antwerp, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.affiliation: Molecular Imaging Center Antwerp (MICA), University of Antwerp, Antwerp (Wilrijk), Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp (Wilrijk), Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Apers
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp (Wilrijk), Belgium. Electronic address: luc.pieters@uantwerpen.be.
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
mesh_terms: D000470:Alkaloids; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D003078:Colchicine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006027:Glycosides; D041743:Herb-Drug Interactions; D006801:Humans; D019668:Liliaceae / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012639:Seeds; D000093542:Gemcitabine
chemical_list: D000470:Alkaloids; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D006027:Glycosides; D010936:Plant Extracts; D003841:Deoxycytidine; C014419:colchicoside; D003078:Colchicine; D000093542:Gemcitabine
keywords: Colchicaceae; Combination therapy; Gemcitabine; Gloriosa superba; Pancreatic tumours