Melatonin and celecoxib improve the outcomes in hamsters with experimental pancreatic cancer

Abstract

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.

Role of melatonin in the regulation of autophagy and mitophagy: A review

“…The ability of melatonin to inhibit the growth of several tumor cell lines has been repeatedly observed (Leja-Szpak et al, 2010;Jung-Hynes et al, 2010;Padillo et al, 2010;Park et al, 2010). A growing body of evidence implicates melatonin's antioxidant actions in the inhibition of cancer development and growth (Mediavilla et al, 2010).…”

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review

“…Melatonin-dependent growth inhibition of rat hepatoma 7288CTC cells was associated with reduced cAMP levels and, presumably, to reduced phosphorylation of ERK2, a downstream target of 13-HODE [101]. Given that ERK activation is involved in phosphorylating MDM2 [102] and FoxO3a [103], two key apoptotic factors that have been demonstrated to be reduced in their phosphorylated form after melatonin administration [28,104], it could be argued that melatonin exerts a relevant apoptotic effect through a 13-HODE-dependent downregulation of ERK phosphorylation.…”

“…A number of studies have examined the role of melatonin in influencing the growth of experimental pancreatic cancers [104,[107][108][109] and several have evaluated the role of induced apoptosis as a means by which melatonin reduced their growth. Leja-Szpak and co-workers [107] found that melatonin had pro-apoptotic actions on a commonly investigated human pancreatic carcinoma, PANC-1 cells.…”

Melatonin Prevents Chemical-Induced Haemopoietic Cell Death

“…High concentrations of MEL (more than 100 μM) enhance the effect of chemotherapeutic drugs, both in cultured cancer cells [14–19] and in vivo [20,21], suggesting that in particular conditions MEL can be harmful, if not deleterious, for cancer cells.…”