Beneficial properties of melatonin in an experimental model of 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 has antioxidant activity and prevents experimental genotoxicity. However, the effect of melatonin in pancreatic cancer has not been tested. Pancreatic carcinogenesis was induced by N-nitrosobis (2-oxopropyl)amine (BOP) in Syrian hamsters. Melatonin was administered during the BOP-induction phase (12 wk) and/or following the postinduction phase (12 wk). Different parameters of oxidative stress including lipid peroxides (LPO) and antioxidants (superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase) were determined in pancreatic tissue. Also, the presence of atypical hyperplasia (AH), well and moderately differentiated adenomacarcinoma (ADC-WD and ADC-MD, respectively) were studied. The administration of BOP induced an intense oxidative stress and ADC induction in the pancreas. The administration of melatonin during the induction or postinduction phase reduced LPO and improved the antioxidant status, as well as drastically reducing the presence of ADC but some AH remained. In conclusion, treatment with melatonin reduced oxidative damage and cancer nodules induced by BOP in the pancreas.

Effects of Capecitabine and Celecoxib in Experimental Pancreatic Cancer

“…The involvement of oxidative stress has been demonstrated in several experimental models of pancreatic cancer [35,36,37,38,39]. The present study showed that the administration of anti-antiangiogenic (celecoxib) and chemotherapeutic (capecitabine) drugs in monotherapy and combined administration recovered the antioxidant status and reduced the progression of pancreatic adenocarcinomas in an experimental model of pancreatic cancer.…”

“…The induction of pancreatic cancer by BOP has histopathological and biochemical similarities with human pancreatic adenocarinoma [35,36,37,38,40,41,42]. Antioxidant drugs such as octreotide [36], tamoxifen [40], vitamin A, C and E [35] and melatonin [38] have been shown to have antitumoral properties in BOP-induced pancreatic cancer.…”

“…Antioxidant drugs such as octreotide [36], tamoxifen [40], vitamin A, C and E [35] and melatonin [38] have been shown to have antitumoral properties in BOP-induced pancreatic cancer. Phase II clinical trials with capecitabine have already been carried out for the treatment of human pancreatic tumors [21,22,23,24,25,43,44,45,46].…”

Adding a combination of hydroxycitrate and lipoic acid (METABLOC™) to chemotherapy improves effectiveness against tumor development: experimental results and case report

“…However, a recent paper reported that melatonin was efficacious in a Syrian hamster model of pancreatic cancer, where N-nitroso-bis(2-oxopropyl)amine was the inducing agent. The evidence suggested that melatonin's anti-oxidative properties were responsible for the observed effect [50]. Prosure (Abbott) is a proprietary nutritional supplement that is often prescribed to cancer patients in order to assist them in gaining weight and improving their quality of life [51].…”

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

“…They incubated rat pancreatic tumor cells (AR42J) with conventional chemotherapies (5-fluorouracil, cisplatin or doxorubicin) in the presence of melatonin and observed that this treatment caused greater mitochondrial membrane depolarization and an elevated the number of cells that underwent apoptosis relative to cells treated only with the pharmaceutical drugs. Similarly, fewer hamsters injected with N-nitrosobis (2-oxopropyl) amine (BOP) developed pancreatic cancer if they were concurrently given melatonin and those that did develop cancer survived longer [239,240]. The authors attributed the beneficial effects of melatonin to its ability to regulate the cellular redox balance.…”