Drug combinations have shown promise in suppressing drug resistance, improving drug efficacy, and reducing side effects in anticancer therapy. Considering that the anticancer activity of melatonin may be due to its antiproliferative, antioxidant, and immunomodulatory activities, the combined administration of this endogenous indoleamine with anticancer drugs has been extensively explored. This review provides an overview of the advances in the last five years in the anticancer activity of melatonin in combination with synthetic drugs and natural products. Papers on this topic were searched in PubMed, Google Scholar, Cochrane, and Scopus within the period 2018–2024. A total of 47 papers were retrieved showing a synergistic antitumor effect of melatonin combined with different drugs in the treatment of breast, colorectal, prostate, gastric, thyroid, and pancreatic cancer, as well as in head and neck squamous cell carcinoma, melanoma, and glioblastoma. The evidence gathered in this review will contribute to our knowledge of the use of melatonin. In addition, it may allow us to develop novel approaches to the treatment of cancer to be evaluated in preclinical and/or clinical trials.

Glioblastoma is the most aggressive and lethal brain tumor in adults, presenting diffuse brain infiltration, necrosis, and drug resistance. Although new drugs have been approved for recurrent patients, the median survival rate is two years; therefore, new alternatives to treat these patients are required. Previous studies have reported the anticancer activity of albendazole, its active metabolite albendazole sulfoxide, and melatonin; therefore, the present study was performed to evaluate if the combination of melatonin with albendazole or with albendazole sulfoxide induces an additive or synergistic cytotoxic effect on C6 and RG2 rat glioma cells, as well as on U87 human glioblastoma cells. Drug interaction was determined by the Chou–Talalay method. We evaluated the mechanism of cell death by flow cytometry, immunofluorescence, and crystal violet staining. The cytotoxicity of the combinations was mainly synergistic. The combined treatments induced significantly more apoptotic and autophagic cell death on the glioma cell lines. Additionally, albendazole and albendazole sulfoxide inhibited proliferation independently of melatonin. Our data justify continuing with the evaluation of this proposal since the combinations could be a potential strategy to aid in the treatment of glioblastoma.

Up to date, the pharmacological treatment for active neurocysticercosis (NCC) includes only two drugs, praziquantel and albendazole; however, the clinical response is not always successful, due to its low bioavailability; therefore, new approaches are needed. The aim of the present study was to evaluate the pharmacological interaction between praziquantel (PZQ) and oxfendazole (OXF) in vitro ; also, the drug-drug interaction between PZQ and OXF or fenbendazole (FBZ) in vivo using Taenia crassiceps metacestode was assessed. For the in vitro study, the surface of synergistic interaction (SSI) analysis was used to determine the kind of drug interaction between PZQ and OXF. Additionally, morphological and ultrastructural effects were investigated using transmission scanning electron microscopy. For the in vivo study, different doses of PZQ and FBZ or OXF were combined, and the cysticidal effect was determined. In vitro, results showed that 12 combinations exhibited synergism, and four exhibited additive effects. The 1:5 ratio of PZQ and OXF exhibited the highest synergistic effect, with an 11-fold increase in comparison to their theoretical sum. Microscopic observations revealed damage to the tegument and germinal layer; microtriches, flame cells, and muscular fibers were also affected. In vivo, results showed that PZQ + FBZ and PZQ + OXF (ratios 1:4 and 1:1, respectively) exhibited a synergistic reduction of the parasites. The findings of the present study show the potential of these combinations as a pharmacological alternative for cysticercosis treatment. Complementary studies are needed to determine their benefits in the clinical field.