TY - JOUR
T1 - Melatonin and celecoxib improve the outcomes in hamsters with experimental pancreatic cancer
AU - Padillo, Francisco J.
AU - Ruiz-Rabelo, Juan F.
AU - Cruz, Adolfo
AU - Perea, María D.
AU - Tasset, Inmaculada
AU - Montilla, Pedro
AU - Túnez, Isaac
AU - Muntané, Jordi
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin (MEL) has antioxidant activity and prevents experimental genotoxicity. The specific inhibitor of cyclooxygenase-2 (COX-2), celecoxib (CEL), increases the efficacy of chemoradiotherapy in advanced pancreatic cancer. The objective of the study was the comparison and synergic effect of MEL and CEL during either the induction or progression phases of the tumor process, measuring parameters of oxidative stress, number of tumor nodules and survival of animals with pancreatic cancer. Pancreatic cancer was induced by N-nitrosobis (2-oxopropyl)amine) (BOP) in Syrian hamsters. Melatonin and/or CEL were administered during the induction, postinduction as well as during both phases. The presence of tumor nodules were observed macroscopically in pancreatic and splenic areas, and the levels of lipoperoxides (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in pancreatic tissue were measured. The increases in tumor nodules and LPO as well as the reductions in GSH and enzymatic antioxidants in the pancreas induced by BOP were related to a lower survival rate of animals. The administration of MEL exerted a more potent beneficial effect than CEL treatment on the reduction in tumor nodules, oxidative stress and death of experimental BOP-treated animals. The combined treatment only exerted a synergistic beneficial effect when administered during the induction phase. Melatonin by itself had significant beneficial actions in improving the survival of hamsters.
AB - Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin (MEL) has antioxidant activity and prevents experimental genotoxicity. The specific inhibitor of cyclooxygenase-2 (COX-2), celecoxib (CEL), increases the efficacy of chemoradiotherapy in advanced pancreatic cancer. The objective of the study was the comparison and synergic effect of MEL and CEL during either the induction or progression phases of the tumor process, measuring parameters of oxidative stress, number of tumor nodules and survival of animals with pancreatic cancer. Pancreatic cancer was induced by N-nitrosobis (2-oxopropyl)amine) (BOP) in Syrian hamsters. Melatonin and/or CEL were administered during the induction, postinduction as well as during both phases. The presence of tumor nodules were observed macroscopically in pancreatic and splenic areas, and the levels of lipoperoxides (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in pancreatic tissue were measured. The increases in tumor nodules and LPO as well as the reductions in GSH and enzymatic antioxidants in the pancreas induced by BOP were related to a lower survival rate of animals. The administration of MEL exerted a more potent beneficial effect than CEL treatment on the reduction in tumor nodules, oxidative stress and death of experimental BOP-treated animals. The combined treatment only exerted a synergistic beneficial effect when administered during the induction phase. Melatonin by itself had significant beneficial actions in improving the survival of hamsters.
KW - celecoxib
KW - melatonin
KW - oxidative stress
KW - pancreatic cancer
UR - http://www.scopus.com/inward/record.url?scp=77956330076&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956330076&partnerID=8YFLogxK
U2 - 10.1111/j.1600-079X.2010.00791.x
DO - 10.1111/j.1600-079X.2010.00791.x
M3 - Article
C2 - 20626589
AN - SCOPUS:77956330076
SN - 0742-3098
VL - 49
SP - 264
EP - 270
JO - Journal of Pineal Research
JF - Journal of Pineal Research
IS - 3
ER -