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Radiation therapy is commonly applied in breast cancer (BC) patients. However, radioresistance and side effects are limiting factors of this practice. Therefore, studying substances that can enhance the radiation effect and, at the same time, protect normal cells is very relevant. Thus, the aim of this work was to assess the radiosensitizer effect of resveratrol (RV) on BC cells (MCF-7). A high cytotoxic and antiproliferative effect was observed in the treatment with 10 μM of RV + 3 Gy ionizing radiation (IR). Our results indicate that, 24 h after the exposition of cell cultures to RV + IR, an induction of necrosis/senescence has occurred. Furthermore, was observed the activation of extrinsic apoptosis pathway through a decrease of the Bax/Bcl-2 ratio and a high activity of caspase 8. Moreover, our data show that this treatment affected the oxidative cell metabolism, increasing oxidative protein, lipid and membrane damage and also acted to decrease the antioxidant enzymes activity. The antiproliferative effect on 72 h cultures may be associated with a high expression of p53 and an interruption of cell cycle in the S phase. Therefore, our results suggest that RV is a potential radiosensitizer of MCF-7 BC cells.

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Resveratrol is an molecule that provides both anti-inflammatory and antioxidant properties. However, it is unclear whether the basal oxidative state of the cell has any influence on the effects of this compound. In humans, a single nucleotide polymorphism (SNP) is present in the enzyme manganese superoxide dismutase (SOD2), localized in codon 16 (rs4880), which can either be an alanine (A) or valine (V). This SNP causes an imbalance in the cellular levels of SOD2, where AA- and VV-genotypes result in higher or lower enzymatic activity, respectively. Furthermore, the VV-genotype has been associated with high levels of inflammatory cytokines. Here, we examined the effects of a range of resveratrol concentrations on the in vitro activation of human peripheral blood mononuclear cells (PBMCs) carrying different Ala16Val-SOD2 genotypes. Cell proliferation, several oxidative biomarkers and cytokines (IL-1β, IL-6, TNFα, Igγ and IL-10) were analyzed. In addition, the effects of resveratrol on the expression of the sirt1 gene were evaluated by qRT-PCR. After 24 h exposure to resveratrol, A-genotype PBMCs displayed a decrease in cell proliferation, whilst VV-cells contrasted; At 10 µM resveratrol, there was a significant decrease in the production of inflammatory cytokines in A-allele cells; however, VV-cells generally displayed a subtle decrease in these, except for TNFα, which was not affected. In all SOD2 genotypes cells exposed to resveratrol resulted in an upregulation of Sirt1 levels. Together, these results suggest that the effect of resveratrol on human PBMC activation is not universal and is dependent on the Ala16Val-SOD2 SNP.

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Lithium (Li) is a chemical element used for treating and preventing bipolar disorder (BD) and exerts positive effects such as anti-inflammatory effects as well as undesirable side effects. These effects of Li can be influenced by interaction with some nutritional elements. Therefore, we investigated the potential effects of xanthine (caffeine and theobromine) and catechin molecules present in some food beverages broadly consumed worldwide, such as coffee and tea, on Li-induced anti-inflammatory effects. In the present study, we concomitantly exposed RAW 264.7 macrophages to Li, isolated xanthine and catechin molecules, and a xanthine-catechin mixture (XC mixture). We evaluated the effects of these treatments on cell proliferation, cell cycle progression, oxidative and antioxidant marker expression, cytokine levels, gene expression, and GSK-3β enzyme expression. Treatment with the XC mixture potentialized Li-induced anti-inflammatory effects by intensification of the following: GSK-3β inhibitory action, lowering effect on proinflammatory cytokines (IL-1β, IL-6, and TNFα), and increase in the levels of IL-10 that is an anti-inflammatory cytokine. Despite the controversial nature of caffeine consumption by BD patients, these results suggested that consumption of caffeine, in low concentrations, mixed with other bioactive molecules along with Li may be safe.