Breast cancer is one of the most common neoplasms among women. Anticancer strategies using natural formulations and phytotherapies are promising antitumor treatment alternatives. This review assesses the antitumor effects of curcumin on breast cancer reported in preclinical in vitro and in vivo animal models. We used five databases to search for preclinical studies published up to May 2021. The assessments included the effects of curcumin on the proliferation, viability, and apoptosis of breast cancer cell lineages and on tumor volume. In total, 60 articles met the inclusion criteria. Curcumin administered at different concentrations and via different routes of administration inhibited proliferation, decreased viability, and induced apoptosis in human and animal breast cancer cells. Nanoparticle formulations of curcumin administered orally, via implant, and intraperitoneally reduced the tumor volume of human and murine mammary cells in vivo. Moreover, curcumin nanoformulations exert positive effects on tumor growth inhibition in animal models of breast cancer. Further randomized clinical trials are warranted to assess the efficacy and safety of curcumin formulations for clinical use.

Chagas Disease (CD) is one of the leading causes of heart failure and sudden death in Latin America. Treatments with antioxidants have provided promising alternatives to ameliorate CD. However, the specific roles of major reactive oxygen species (ROS) sources, including NADPH-oxidase 2 (NOX2), mitochondrial-derived ROS and nitric oxide (NO) in the progression or resolution of CD are yet to be elucidated. We used C57BL/6 (WT) and a gp91^PHOX knockout mice (PHOX^-/-), lacking functional NOX2, to investigate the effects of ablation of NOX2-derived ROS production on the outcome of acute chagasic cardiomyopathy. Infected PHOX^-/- cardiomyocytes displayed an overall pro-arrhythmic phenotype, notably with higher arrhythmia incidence on ECG that was followed by higher number of early afterdepolarizations (EAD) and 2.5-fold increase in action potential (AP) duration alternans, compared to AP from infected WT mice. Furthermore, infected PHOX^-/- cardiomyocytes display increased diastolic [Ca²⁺], aberrant Ca²⁺ transient and reduced Ca²⁺ transient amplitude. Cardiomyocyte contraction is reduced in infected WT and PHOX^-/- mice, to a similar extent. Nevertheless, only infected PHOX^-/- isolated cardiomyocytes displayed significant increase in non-triggered extra contractions (appearing in ~75% of cells). Electro-mechanical remodeling of infected PHOX^-/—cardiomyocytes is associated with increase in NO and mitochondria-derived ROS production. Notably, EADs, AP duration alternans and in vivo arrhythmias were reverted by pre-incubation with nitric oxide synthase inhibitor L-NAME. Overall our data show for the first time that lack of NOX2-derived ROS promoted a pro-arrhythmic phenotype in the heart, in which the crosstalk between ROS and NO could play an important role in regulating cardiomyocyte electro-mechanical function during acute CD. Future studies designed to evaluate the potential role of NOX2-derived ROS in the chronic phase of CD could open new and more specific therapeutic strategies to treat CD and prevent deaths due to heart complications. Chagas disease (CD) is an important neglected disease mainly found in developing countries. However, due to migration flow, it became a health problem worldwide. Infection by Trypanosoma cruzi typically occurs after an infected Triatominae vector takes a blood meal and leaves parasites in its feces nearby the bite wound. Two distinct symptomatic stages of CD are typical, an acute phase that lasts few weeks and a chronic stage, that can last for 10–30 years after infection, and may lead to severe cardiac arrhythmias and death. Here, we used an experimental model of acute CD to study the involvement of reactive oxygen species (ROS) and nitric oxide (NO) with structural and functional remodeling of cardiomyocytes and the heart. We found that an unbalanced production of two sources of reactive species may worsen cellular electromechanical dysfunction, leading to more severe arrhythmias despite additional structural changes in heart tissue. Interestingly, it was possible to attenuate the unbalanced relationship between ROS and NO by inhibition of NO production, leading to recovery of electrical function of heart cells and ameliorating in vivo heart arrhythmia. Thus, in the long term, our study may contribute to the development of new therapies to individuals with the cardiac form of CD.