Caffeine improves the cytotoxic effect of dacarbazine on B16F10 murine melanoma cells.

OBJECTIVE: Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to investigate caffeine's ability to enhance the effects of dacarbazine in vitro. MATERIALS AND METHODS: Murine melanoma B16F10 cells were treated 24 h with 1-40 µM caffeine. We evaluated cytotoxicity, DNA damage, apoptosis, and oxidative lesion induced by dacarbazine associated with caffeine. The metabolization of these drugs, as well as immunocytochemical labeling, were also evaluated. CONCLUSIONS: The pre-treatment with caffeine showed to be more effective. Caffeine potentiated dacarbazine-induced cytotoxic effects by increasing dacarbazine biotransformation, apoptosis, DNA damage, and malondialdehyde levels; also, caffeine reduced Ki67 and ERK1/2 nuclear labeling and increased p53 labeling in B16F10 cells. In our experiment, caffeine promoted modifications associated with dacarbazine metabolism by viable cells potentiating this antineoplastic drug. These promising results should be further evaluated in experimental models in vivo.

Chimarrão consumption and prognostic factors in breast cancer: Correlation with antioxidants and blood caffeine levels.

Breast cancer is the second most common malignancy among women. Ilex paraguariensis A. St. Hil, known as yerba mate, is widely consumed in southern Brazil as a hot infusion drink known as chimarrão. This herb has a complex chemical composition and is rich in antioxidants, which may interfere in the course of chronic inflammatory diseases as breast cancer. This study investigated the impact of chimarrão consumption on the clinicopathological profile of women with breast cancer attended at Francisco Beltrão Cancer Hospital, Paraná, Brazil. Blood antioxidants and caffeine profiles were assessed. Decreases in reduced glutathione and metallothionein levels, and increase in catalase activity were observed among breast cancer patients that were chimarrão consumers. The levels of circulating caffeine in breast cancer patients with luminal A tumors were higher than those in patients with luminal B and HER-2 subtypes. Furthermore, overweight patients presented higher caffeine levels than the eutrophic ones. It was found positive associations between chimarrão intake and high body mass index, and chimarrão intake and menopause at diagnosis. Altogether, these findings suggest that chimarrão consumption affects the blood antioxidants of breast cancer patients, and that the caffeine present in this mixture may favor the development of tumor of good prognosis. HIGHLIGHTS: Chimarrão consumption may affect the course of chronic inflammatory diseases, as breast cancer. Chimarrão intake changed blood antioxidants in breast cancer patients who were current consumers when compared to the non-consumers ones. High levels of caffeine were detected in patients bearing luminal A tumors, suggesting a protective role.

Protective effect of metformin in an aberrant crypt foci model induced by 1,2-dimethylhydrazine: Modulation of oxidative stress and inflammatory process.

Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET-an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.

Cytotoxicity of citral against melanoma cells: The involvement of oxidative stress generation and cell growth protein reduction.

Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling. To test this hypothesis, we investigated the antiproliferative and cytotoxic effects of citral on B16F10 murine melanoma cells evaluating its effects on cellular oxidative stress, DNA damage, cell death, and important signaling pathways, as these pathways, namely, extracellular signal-regulated kinases 1/2 (ERK1/2), AKT, and phosphatidylinositol-3 kinase, are involved in cell proliferation and differentiation. The p53 and nuclear factor kappa B were also investigated due to their ability to respond to intracellular stress. We observed that citral exerted antiproliferative and cytotoxic effects in B16F10; induced oxidative stress, DNA lesions, and p53 nuclear translocation; and reduced nitric oxide levels and nuclear factor kappa B, ERK1/2, and AKT. To investigate citral specificity, we used non-neoplastic human and murine cells, HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts), and observed that although citral effects were not specific for cancer cells, non-neoplastic cells were more resistant to citral than B16F10. These findings highlight the potential clinical utility of citral in melanoma, with a mechanism of action involving the oxidative stress generation, nitric oxide depletion, and interference in signaling pathways related to cell proliferation.

Glyphosate as a Food Contaminant: Main Sources, Detection Levels, and Implications for Human and Public Health.

Glyphosate is a broad-spectrum pesticide that has become the most widely used herbicide globally. However, concerns have risen regarding its potential health impacts due to food contamination. Studies have detected glyphosate in human blood and urine samples, indicating human exposure and its persistence in the organism. A growing body of literature has reported the health risks concerning glyphosate exposure, suggesting that the daily intake of contaminated food and water poses a public health concern. Furthermore, countries with high glyphosate usage and lenient regulations regarding food and water contamination may face more severe consequences. In this context, in this review, we examined the literature regarding food contamination by glyphosate, discussed its detection methods, and highlighted its risks to human health.

Monitoring residues of pesticides in food in Brazil: A multiscale analysis of the main contaminants, dietary cancer risk estimative and mechanisms associated.

Introduction: Pesticides pose a risk for cancer development and progression. People are continuously exposed to such substances by several routes, including daily intake of contaminated food and water, especially in countries that are highly pesticide consumers and have very permissive legislation about pesticide contamination as Brazil. This work investigated the relationship among pesticides, food contamination, and dietary cancer risk. Methods: Analyzed two social reports from the Brazilian Government: the Program for Analysis of Residues of Pesticides in Food (PARA) and The National Program for Control of Waste and Contaminants (PNCRC). Results and discussion: First, we characterized the main pesticide residues detected over the maximum limits allowed by legislation or those prohibited for use in food samples analyzed across the country. Based on this list, we estimated the dietary cancer risks for some of the selected pesticides. Finally, we searched for data about dietary cancer risks and carcinogenic mechanisms of each pesticide. We also provided a critical analysis concerning the pesticide scenario in Brazil, aiming to discuss the food contamination levels observed from a geographical, political, and public health perspective. Exposures to pesticides in Brazil violate a range of human rights when food and water for human consumption are contaminated.

Patterns of Cell Death Induced by Thiohydantoins in Human MCF-7 Breast Cancer Cells.

BACKGROUND: Conventional therapies for breast cancer are still a challenge due to cytotoxic drugs not being highly effective with significant adverse effects. Thiohydantoins are biologically active heterocyclic compounds reported for several biological activities, including anticarcinogenic properties, etc. This work aims to assess the use of thiohydantoin as a potential antitumor agent against MCF-7 breast cancer cells. METHODS: MTT and neutral red assays were used to assess the possible cytotoxic activity of compounds against MCF-7 cells. Cell volume measurement and analysis were performed by flow cytometry. Fluorescence analysis was carried out to determine patterns of cell death induced by thiohydantoins. RESULTS: The treatment with micromolar doses of thiohydantoins promoted a decrease in the viability of MCF-7 breast tumor cells. An increase in the ROS and NO production, reduction in cell volume, loss of membrane integrity, mitochondrial depolarization, and increased fluorescence for annexin-V and caspase-3 were also observed. These findings indicate cell death by apoptosis and increased autophagic vacuoles, stopping the cell cycle in the G1/ G0 phase. CONCLUSION: Our results indicate that thiohydantoins are cytotoxic to breast tumor cells, and this effect is linked to the increase in ROS production. This phenomenon changes tumorigenic pathways, which halt the cell cycle in G1/G0. This is an essential checkpoint for DNA errors, which may have altered how cells produce energy, causing a decrease in mitochondrial viability and thus leading to the apoptotic process. Furthermore, the results indicate increased autophagy, a vital process linked to a decrease in lysosomal viability and thus considered a cell death and tumor suppression mechanism.

Grandiflorenic acid from Wedelia trilobata plant induces apoptosis and autophagy cell death in breast adenocarcinoma (MCF7), lung carcinoma (A549), and hepatocellular carcinoma (HuH7.5) cells lines.

INTRODUCTION: Wedelia trilobata (Sphagneticola trilobata) is a plant used in this popular medicine for treating infectious, sores and swellings in some rural communities, and their extract has antioxidant, anti-inflammatory, antitumor and hepatoprotective effect. Cancer is a molecularly heterogeneous disease caused by environmental and, genetic factors, among others. Since the complexity of the disease leads to low response rates to the different treatments used, it is necessary to find alternative drugs aimed at its control. The objective of our study was to assess whether grandiflorenic acid (GFA) has antitumor activity on breast (MCF7), liver (HuH7.5), and lung (A549) tumor cell lines. METHODS: We used cell integrity assessment methods to assess whether (GFA) would be cytotoxic for tumor cell lines at doses ranging from and the pattern of death involved in this effect. RESULTS: Treatment using GFA significantly inhibited cell proliferation in the three studied cells, followed by a decrease in cell size. The assessment of the death mechanisms showed the treatments increased the production of reactive oxygen species, caused exposure of phosphatidylserine, depolarization of the mitochondrial membrane, and, decrease plasma membrane integrity, indicating mechanisms related to apoptosis. Besides, we found the formation of autophagy vacuoles in our tests. CONCLUSION: Finally, our study found the effect of GFA on breast (MCF7), lung (A549), and liver (HuH7.5) tumor cell lines induce cytotoxicity and patterns of death associated with apoptosis and autophagy, and oxidative stress generation plays a role in these two pathways of cell death. Thus, this study revealed GFA exhibits anti-cancer activity in vitro and could help future studies to improve strategies for cancer treatment with involving natural compounds.