title: In vitro and in vivo investigations on the antitumour activity of Chelidonium majus.
abstract: BACKGROUND
  Chelidonium majus L. (Papaveraceae) (greater celandine) is a medicinal herb that is widely spread in Europe. Antitumoural activity has been reported for C. majus extracts.
  
  
  OBJECTIVE
  To investigate the antitumour activity of a C. majus extract in vitro and in vivo.
  
  
  METHODS
  Cytotoxic effects of C. majus extracts were evaluated on human cancer cell lines, i.e. PANC-1 (pancreas cancer), HT-29 (colon cancer), MDA-MB-231 (breast cancer), PC-EM005 and PC-EM002 (primary endometrium cancer cells), and PANC02 (murine pancreatic adenocarcinoma cells). A preliminary in vivo study was performed to evaluate the effect of a defatted C. majus extract and Ukrain(TM) in a highly metastatic murine pancreatic model.
  
  
  METHODS
  Chelidonium majus L. herb containing 1.26% (dry weight) of total alkaloids expressed as chelidonine was used to prepare an 80% ethanolic extract (CM2). This crude extract was then defatted with n-hexane, resulting in a defatted C. majus extract (CM2B). Cytotoxic effects of the two extracts (CM2 and CM2B) were evaluated on human and murine cell lines in vitro. CM2B and Ukrain(TM) were evaluated in a highly metastatic murine pancreatic model.
  
  
  RESULTS
  Four main benzylisoquinoline alkaloids were identified in CM2B, i.e. chelidonine, sanguinarine, chelerythrine and protopine, using HPLC-UV. CM2 showed a high cytotoxic activity against PANC-1 (IC50, 20.7 µg/ml) and HT-29 (IC50, 20.6 µg/ml), and a moderate cytotoxic activity against MDA-MB-231 (IC50, 73.9 µg/ml). CM2 as well as CM2B showed a moderate to high cytotoxic activity against the PANC02 cell line (IC50, 34.4 and 36.0 µg/ml). Low to almost no cytotoxic effect was observed on primary endometrium cancer cells PC-EM005, PC-EM002 and on normal fibroblast cells 3T3, when treated with CM2B. Significantly less metastases were counted in mice treated with 1.2 mg/kg CM2B, but not with 3.6 mg/kg Ukrain(TM), compared to the control group. The extract, however, did not affect the weight of the primary tumours.
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Rica
authors.initials: R
authors.lastname: Capistrano I
authors.affiliation: Center for Oncological Research (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Wouters
authors.affiliation: Center for Oncological Research (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Lardon
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine New York, NY, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gravekamp
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, 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, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: luc.pieters@uantwerpen.be.
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000494:pharmacology; D001600:Berberine Alkaloids / Q000494:pharmacology; D045744:Cell Line, Tumor; D028281:Chelidonium / Q000737:chemistry*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D007546:Isoquinolines; D010936:Plant Extracts; C062047:chelidonine; C005705:sanguinarine; C016299:chelerythrine; C009093:protopine
keywords: Chelidonium majus L.; Greater celandine; In vitro cytotoxicity; In vivo antitumor activity; Papaveraceae