Improvement of Capecitabine Antitumoral Activity by Melatonin in Pancreatic Cancer
Department of Surgery, Reina Sofia University Hospital, Córdoba, Spain. Pancreas
(Impact Factor: 2.96).
12/2010; 40(3):410-4. DOI: 10.1097/MPA.0b013e318201ca4f
The purpose of our study was to evaluate the effects of the addition of melatonin and capecitabine on experimental pancreatic cancer.
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.
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.
The combined administration of capecitabine and melatonin provided an improvement in antioxidant status as well as a synergistic antitumoral effect in experimental pancreatic cancer.
Available from: online.journals.tubitak.gov.tr
- "An evaluation of pathological tumor evolution and oxidative stress markers in pancreatic tissue was carried out in Syrian hamsters. In that study, melatonin exerted beneficial effects that were associated with a decrease in lipoperoxide levels and increased antioxidant activity in the pancreatic tissue (Ruiz-Rabelo et al., 2011). Previously it had been shown that celecoxib, a specific inhibitor of cyclooxygenase-2, induced a reduction in tumor nodules, oxidative stress, and death of Syrian hamsters with developed experimental pancreatic cancer. "
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ABSTRACT: Melatonin, a derivative of the amino acid tryptophan, was initially thought to be mainly produced and secreted by the pineal gland; with time, it was also found in other tissues and organs, and even in plants. Since its discovery, the study of the role of the indole in cellular homeostasis has generated impressive data, which have led researchers to a common idea regarding the positive actions of melatonin in health. The uncontrolled production of free radicals in cellular systems leads to the situation termed oxidative stress, which has been signaled as the basis of disease and aging. In the exocrine pancreas, as in other parts of the body, a daily confrontation takes place against oxidative stress. The major signaling mechanisms controlling the physiology of the gland are affected under this situation. Because a love-hate relationship involving mitochondria and oxidative stress has been considered the basis of disease, any physiological regulator that sets hands on the system as a pacemaker will be determinant for the health’s fate. Here we present an overview of the recent findings regarding the protective role of melatonin on the function of the exocrine pancreas, paying attention to the role of Ca2+ signaling and the involvement of mitochondria.
Available from: E.J. J Sánchez-Barceló
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ABSTRACT: INTRODUCTION: The possible oncostatic properties of melatonin on different types of neoplasias have been studied especially in hormone-dependent adenocarcinomas. Despite the promising results of these experimental investigations, the use of melatonin in breast cancer treatment in humans is still uncommon. AREAS COVERED: This article reviews the usefulness of this indoleamine for specific aspects of breast cancer management, particularly in reference to melatonin's antiestrogenic and antioxidant properties: i) treatments oriented to breast cancer prevention, especially when the risk factors are obesity, steroid hormone treatment or chronodisruption by exposure to light at night (LAN); ii) treatment of the side effects associated with chemo- or radiotherapy. EXPERT OPINION: The clinical utility of melatonin depends on the appropriate identification of its actions. Because of its SERM (selective estrogen receptor modulators) and SEEM (selective estrogen enzyme modulators) properties, and its virtual absence of contraindications, melatonin could be an excellent adjuvant with the drugs currently used for breast cancer prevention (antiestrogens and antiaromatases). The antioxidant actions also make melatonin a suitable treatment to reduce oxidative stress associated with chemotherapy, especially with anthracyclines, and radiotherapy.
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ABSTRACT: Melatonin influences a number of physiological processes and is believed to play an antitumoral role in several types of cancers, but its impact on pancreatic cancer is not fully clarified. The growth inhibitory effect of melatonin on pancreatic cancer cell line SW-1990 was detected in vitro and in vivo. Annexin V/PI assay was applied to detect apoptosis and necrosis in SW-1990 cells. Changes of Bcl-2 and Bax expression were investigated by RT-PCR and Western blot. An obvious growth inhibition was found in SW-1990 after melatonin or combined treatment with melatonin and gemicitabine through both apoptosis and necrosis in vitro, and also found in transplanted tumors in nude mice. RT-PCR and Western blot showed that Bcl-2 expression was downregulated, while Bax expression was upregulated, after melatonin treatment. Melatonin may be a pro-apoptotic and pro-necrotic agent for pancreatic cancer cells via its modulation of Bcl-2/Bax balance.
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