title: Improvement of capecitabine antitumoral activity by melatonin in pancreatic cancer.
abstract: OBJECTIVE
  The purpose of our study was to evaluate the effects of the addition of melatonin and capecitabine on experimental pancreatic cancer.
  
  
  METHODS
  Fifty Syrian hamsters were randomized in 5 groups: group 1: no tumor induction (control group); group 2: tumor induction with BOP [N-nitrosobis(2-oxopropyl) amine]; group 3: tumor induction with BOP and melatonin administration; group 4: tumor induction with BOP and capecitabine administration; and group 5: tumor induction with BOP and administration of combined capecitabine and melatonin therapy. The evaluation of pathological tumor evolution and oxidative stress markers in pancreatic tissue was carried out.
  
  
  RESULTS
  All animals under BOP exposure presented poorly or moderately differentiated pancreatic adenocarcinoma associated with increased lipoperoxide levels and decreased antioxidant activity in pancreatic tissue. Pancreatic cancer was shown in only 66% of the capecitabine-treated group and 33% of melatonin-treated group (P < 0.05), most of them moderately differentiated adenocarcinoma. When capecitabine and melatonin were combined, a well-differentiated pancreatic adenocarcinoma was observed in 10% of animals. The beneficial effect was associated with a decrease in lipoperoxide levels and increased antioxidant activity in pancreatic tissue.
  
  
  CONCLUSIONS
  The combined administration of capecitabine and melatonin provided an improvement in antioxidant status as well as a synergistic antitumoral effect in experimental pancreatic cancer.
authors.affiliation: Department of Surgery, Reina Sofia University Hospital, Córdoba, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz-Rabelo
authors.forename: Reyes
authors.initials: R
authors.lastname: Vázquez
authors.forename: Alvaro
authors.initials: A
authors.lastname: Arjona
authors.forename: Dolores
authors.initials: D
authors.lastname: Perea
authors.forename: Pedro
authors.initials: P
authors.lastname: Montilla
authors.forename: Isaac
authors.initials: I
authors.lastname: Túnez
authors.forename: Jordi
authors.initials: J
authors.lastname: Muntané
authors.forename: Javier
authors.initials: J
authors.lastname: Padillo
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D000069287:Capecitabine; D006224:Cricetinae; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008647:Mesocricetus; D009602:Nitrosamines / Q000633:toxicity; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011355:Prodrugs / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D008054:Lipid Peroxides; D009602:Nitrosamines; D011355:Prodrugs; D003841:Deoxycytidine; C013622:nitrosobis(2-oxopropyl)amine; D000069287:Capecitabine; D008550:Melatonin; D005472:Fluorouracil