RESUMO

Renal neoplasms are highlighted as one of the 10 most common types of cancer. Renal cell carcinoma (RCC) is the most common type of renal cancer, considered the seventh most common type of cancer in the Western world. The most frequently altered genes described as altered are VHL, PBRM1, SETD2, KDM5C, PTEN, BAP1, mTOR, TP53, TCEB1 (ELOC), SMARCA4, ARID1A, and PIK3CA. RCC therapies can be classified in three groups: monoclonal antibodies, tyrosine kinase inhibitors, and mTOR inhibitors. Besides, there are targeted agents to treat RCC. However, frequently patients present side effects and resistance. Even though many multidrug resistance mechanisms already have been reported to RCC, studies focused on revealing new biomarkers as well as more effective antitumor therapies with no or low side effects are very important. Some studies reported that natural products, such as honey, epigallocatechin-3-gallate (EGCG), curcumin, resveratrol, and englerin A showed antitumor activity against RCC. Moreover, nanoscience is another strategy to improve RCC treatment and reduce the side effects due to the improvement in pharmacokinetics and reduction of toxicities of chemotherapies. Taking this into account, we conducted a systemic review of recent research findings on RCC hallmarks, drug resistance, and adjuvant therapies. In conclusion, a range of studies reported that RCC is characterized by high incidence and increased mortality rates because of the development of resistance to standard therapies. Given the importance of improving RCC treatment and reducing adverse effects, nanoscience and natural products can be included in therapeutic strategies.

RESUMO

Melanoma frequently presents a poor chemotherapy response. In this scenario, investigations for new therapies are essential. Thus, cocoa is highlighted in this area since it presents many biological properties. This study investigated the anticarcinogenic activity of cocoa in melanoma cell lines (A-375 and B16-F10). Melanoma and fibroblast (HFF-1) cell lines were exposed to different concentrations of cocoa seeds (30 to 2000 ug/ml) at 24 and 72 h. Cocoa was also associated with paclitaxel IC50. We conducted viability, proliferation, and oxidative stress analyses. Our findings suggested that cocoa isolated, at almost all concentrations tested, was able to reduce viability and proliferation of B16-F10 cells and proliferation of A-375 cells via oxidative stress increasing. Also, cocoa caused no damage in fibroblast cells. Moreover, cocoa increased paclitaxel activity on A-375 by reducing cell proliferation and increasing oxidative stress. Therefore, the results highlight cocoa as a potent selective adjuvant anticancer agent against melanoma. PRACTICAL APPLICATIONS: In conclusion, more studies should be performed to deeply explore this remarkable action of cocoa as a an promising adjuvant to enhance chemotherapy.

Assuntos

Antineoplásicos , Cacau , Melanoma , Linhagem Celular Tumoral , Melanoma/tratamento farmacológico , Estresse Oxidativo , Paclitaxel/farmacologia

RESUMO

Randia ferox is a Brazilian native species used in folk medicine. Scientific information regarding the toxicology and phytochemistry of this plant remains unclear. We aimed to produce a R. ferox extract, identify its chemical matrix, and evaluate its safety profile. The extract chemical composition was accessed through UHPLC-MS/MS. Mononuclear cells, erythrocytes, fibroblasts, macrophages, and kidney cells were subjected to extract concentration-response curve testing. The cellular viability, proliferation, dsDNA release, reactive oxygen species (ROS), nitric oxide (NO), hemolysis, and DNA damage were determined. Ten molecules were found in the extract matrix. Most of the tested concentrations can be considered safe. Cellular viability, proliferation, dsDNA release, and NO remained at similar levels to the control. The extract increased ROS in macrophages. None of the tested concentrations induced DNA damage or hemolysis. The data suggest R. ferox extract contains several bioactive molecules and has a safety profile in vitro.

Assuntos

Rubiaceae , Espectrometria de Massas em Tandem , Dano ao DNA , Hemólise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio

RESUMO

Cancer is considered a multifactorial disease and its development could be associated with several factors, for example, rotenone exposition. Unfortunately, many cancers are resistant to chemotherapy, as cervical cancer. Regarding this, lemongrass is a remarkable natural product that presents antioxidant and anticancer activities, which could show therapeutic action against rotenone and cervical cancer. Thus, this study aimed to investigate the antioxidant and anticancer action of lemongrass. An in vitro study was conducted using VERO (kidney cells) and SiHa cell lines (cervical cancer cells). VERO cells were exposed to rotenone and lemongrass extract for 24 and 72 h. While SiHa cells were exposed to lemongrass isolated and associated to chemotherapy, 5-fluorouracil, during 24 and 48 h. After, levels of viability, proliferation, and oxidative metabolism were determined. The results showed that lemongrass presents antioxidant activity on VERO cells by increasing cell viability and proliferation and decreasing oxidative stress caused by rotenone. Moreover, lemongrass showed anticancer activity by decreasing cell viability and increasing oxidative stress parameters on SiHa. Besides, lemongrass had no alteration in the chemotherapy activity. Therefore, this study revealed that lemongrass presents antioxidant and anticancer activity since it can protect against the cytotoxicity of rotenone and reduce the cell viability of cervical cancer.

Assuntos

Cymbopogon , Neoplasias do Colo do Útero , Animais , Antioxidantes/farmacologia , Chlorocebus aethiops , Feminino , Humanos , Rotenona , Neoplasias do Colo do Útero/tratamento farmacológico , Células Vero

RESUMO

Photobiomodulation is widely used in clinical practice, and there is increasing interest in using this tool to treat numerous dysfunctions in living organisms. Therefore, this study aimed to verify the action of blue and red light-emitting diode light in cells. Human fibroblast cell line (HFF-1) were irradiated by blue (470 nm) or red (658 nm) light at doses of 4 and 18 J/cm2, respectively. Laboratory analyses were carried out to check for viability, proliferation, cell death, and the formation of reactive oxygen and nitric oxide species. The blue light demonstrated cell protection potential by reducing free radical formation and protecting the cell membrane by decreasing double-stranded DNA strands. On the other hand, the red light showed less potential for cell protection due to the risk of associating more significant nitric oxide formation with increased reactive oxygen species formation, in addition to having a greater amount of extracellular DNA. Cell damage prevention is a potential beneficial effect of blue light at 18 J/cm2. Despite the consolidated effects of red light in treating wounds, there was a potential toxic effect of this wavelength in the doses studied. Given the above, new studies relating these parameters with pathological cells or aggressors that simulate damage may offer results that can better support clinical practice.

Assuntos

Fibroblastos , Dermatopatias , Linhagem Celular , Proliferação de Células , Humanos , Luz

RESUMO

Oxidative stress is known to be involved in development of numerous diseases including cardiovascular, respiratory, renal, kidney and cancer. Thus, investigations that mimic oxidative stress in vitro may play an important role to find new strategies to control oxidative stress and subsequent consequences are important. Rotenone, widely used as a pesticide has been used as a model to simulate oxidative stress. However, this chemical was found to produce several diseases. Therefore, the aim of this study was to investigate the antioxidant and cytoprotective effect of avocado (Persea americana Mill) extract and oil in monkey kidney epithelial cells (VERO) exposed to rotenone. VERO cells were exposed to IC50 of rotenone in conjunction with different concentrations of avocado extract and oil (ranging from 1 to 1000 µg/ml), for 24 hr. Subsequently, cell viability and oxidative metabolism were assessed. Data demonstrated that avocado extract and oil in the presence of rotenone increased cellular viability at all tested concentrations compared to cells exposed only to rotenone. In addition, extract and avocado oil exhibited antioxidant action as evidenced by decreased levels of reactive oxygen species (ROS), superoxide ion, and lipid peroxidation, generated by rotenone. Further, avocado extract and oil appeared to be safe, since these compounds did not affect cell viability and or generate oxidative stress. Therefore, avocado appears to display a promising antioxidant potential by decreasing oxidative stress.

Assuntos

Antioxidantes/farmacologia , Crioprotetores/farmacologia , Inseticidas/efeitos adversos , Persea/química , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Rotenona/efeitos adversos , Animais , Chlorocebus aethiops , Extratos Vegetais/química , Óleos de Plantas/química , Células Vero

RESUMO

Neurological disorders have been demonstrated to be associated with mitochondrial dysfunction. This impairment may lead to oxidative stress and neuroinflammation, specifically promoted by NLRP3 expression. Açaí (Euterpe oleracea Mart.) has been studied in this field, since it presents important biological activities. We investigated açaí extract's anti-neuroinflammatory capacity, through NLRP3 inflammasome modulation. Microglia (EOC 13.31) were exposed to LPS and nigericin, as agents of inflammatory induction, and treated with açaí extract. Additionally, we used lithium (Li) as an anti-inflammatory control. Three different experiment models were conducted: (1) isolated NLRP3 priming and activation signals; (2) combined NLRP3 priming and activation signals followed by açaí extract as a therapeutic agent; and (3) combined NLRP3 priming and activation signals with açaí extract as a preventive agent. Cells exposed to 0.1 µg/mL of LPS presented high proliferation and increased levels of NO, and ROS, while 0.1 µg/mL of açaí extract was capable to reduce cellular proliferation and recover levels of NO and ROS. Primed and activated cells presented increased levels of NLRP3, caspase-1, and IL-1ß, while açaí, Li, and orientin treatments reversed this impairment. We found that açaí, Li, and orientin were effective prophylactic treatments. Preventative treatment with Li and orientin was unable to avoid overexpression of IL-1ß compared to the positive control. However, orientin downregulated NLRP3 and caspase-1. Lastly, primed and activated cells impaired ATP production, which was prevented by pre-treatment with açaí, Li, and orientin. In conclusion, we suggest that açaí could be a potential agent to treat or prevent neuropsychiatric diseases related to neuroinflammation.

Assuntos

Anti-Inflamatórios/farmacologia , Euterpe , Microglia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Caspase 1/metabolismo , Proliferação de Células/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , Nigericina/farmacologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo

RESUMO

Solanum sessiliflorum is an Amazonian fruit (cubiu) that has been domesticated since pre-Colombian era. It is also used in folk medicine to treat some clinical conditions. This investigation chemically characterized and analyzed the in vitro antioxidant and antitumoral effect of a cubiu pulp/seed hydroalcoholic extract. Cubiu extract was chemically characterized by high-performance liquid chromatography with diode array detector (HPLC-DAD), its antioxidant capacity measured by 2.2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the following complementary in vitro protocols were performed: (1) cytoprotective effect of cubiu on human peripheral blood mononuclear cells (PBMCs) exposed to H2O2, a genotoxic and procarcinogen molecule; (2) effect of cubiu on low density lipoproteins oxidation; and (3) cytotoxic and antiproliferative effect on breast (MCF-7) and colorectal (HT-29) cancer cell lines. Biochemical and flow cytometry analyses were conducted in these protocols. Cubiu extract presented high concentrations of caffeic and gallic acids, beta-carotene, catechin, quercetin, and rutin, and its antioxidant capacity was confirmed. Cubiu attenuated H2O2 cytotoxicity on PBMCs, presented lowering effect on LDL oxidation, and induced mortality and proliferative inhibition of colorectal cancer cells. In cancer cells, cubiu extract at 10 µg/mL showed similar effects to 5-fluorouracil chemo drug reducing its viability and frequency of S-phase, indicating that cells are undergoing mitosis. In summary, despite the limitations of in vitro protocols, our results suggest that cubiu has several biological properties that affect human health.

Assuntos

Antioxidantes/farmacologia , Frutas/química , Extratos Vegetais/farmacologia , Solanum/química , Células Cultivadas , Humanos , Peróxido de Hidrogênio , Leucócitos Mononucleares/efeitos dos fármacos , Células MCF-7 , Compostos Fitoquímicos/farmacologia

RESUMO

Mesenchymal stem cells are a population of somatic cells found in several tissues of an adult organism, including adipose tissue. Reactive oxygen species (ROS) can cause cellular alterations, including mutagenesis and genomic instability and the development of diseases. Thus, it is important to understand ROS-induced damage to cell macromolecules such as DNA, proteins, and lipids. In this study, we investigated oxidative stress rates and viability of adipose tissue-derived mesenchymal stem cells (ADSCs) from the greater omentum of rabbits. Cell cultures were analyzed at different passages (1-5) using the dichlorofluorescein acetate assay for measuring ROS production and cell viability tests. ROS levels were highest at passage 2 and cell viability was highest at passage 4.(AU)

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Células-tronco mesenquimais são uma população de células somáticas encontradas em vários tecidos de um organismo adulto, incluindo o tecido adiposo. Espécies reativas de oxigênio (ROS) podem causar alterações celulares, incluindo mutagênese e instabilidade genômica e o desenvolvimento de doenças. Assim, é importante entender o dano induzido pelas EROs às macromoléculas celulares, como DNA, proteínas e lipídios. Neste estudo, investigamos as taxas de estresse oxidativo e viabilidade de células-tronco mesenquimais derivadas do tecido adiposo (ADSCs) a partir do omento maior de coelhos. As culturas celulares foram analisadas em diferentes passagens (1-5) utilizando o ensaio de acetato de diclorofluoresceína para medir a produção de ROS e testes de viabilidade celular. Os níveis de EROs foram mais altos na 2ª passagem e a viabilidade celular foi maior na 4ª passagem.(AU)

Assuntos

Animais , Coelhos , Células-Tronco Mesenquimais , Estresse Oxidativo , Sobrevivência Celular , Coelhos , Espécies Reativas de Oxigênio , Terapia Baseada em Transplante de Células e Tecidos

RESUMO

The purpose of this study was to investigate some possible mechanisms underlying the in vitro antitumor activity of tea tree oil (TTO) on human and mouse breast cancer cells (MCF-7 and 4T1, respectively) and its cytotoxicity on fibroblasts (HFF-1) and on peripheral blood mononuclear cells (PBMCs). TTO High-Resolution Gas Chromatography (HRGC) showed seventeen main constituents, such as Terpinen-4-ol, γ-Terpinene, and α-Terpinene. High TTO concentrations (≥ 600 µg/mL) showed a remarkable antitumor activity, decreasing cell viability and cell proliferation of MCF-7 and 4T1 cells. TTO at 300 µg/mL increased the number of MCF-7 cells in the early stages of apoptosis and increased the BAX/BCL-2 genes ratio. TTO, mainly at 300 µg/mL, decreased cell growth and arrested MCF-7 cells in the S phase of the cell cycle. Lower antitumor concentrations (≤300 µg/mL) evaluated in MCF-7 and 4T1 cells were not cytotoxic to PBMCs and HFF-1. Also, TTO (300 µg/mL) was able to induce cell proliferation in fibroblasts after 72 h, indicating non-cytotoxic effect in these cells. TTO exhibited in vitro antitumor effect on MCF-7 and 4T1 cells by decreasing cell viability and modulating apoptotic pathways and cell cycle arrestment of MCF-7 cells. In this sense, our study provides new perspectives on the potential use of TTO for the development of new alternative therapies to treat topically locally advanced breast cancer (LABC).

Assuntos

Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Fibroblastos/citologia , Leucócitos Mononucleares/citologia , Óleo de Melaleuca/farmacologia , Adulto , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Modelos Biológicos , Adulto Jovem

RESUMO

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.

Assuntos

Neoplasias da Mama/tratamento farmacológico , Radiossensibilizantes/farmacologia , Estilbenos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo

RESUMO

The aim of this study was to evaluate the potential use of a DNA comet assay, DNA fragmentation fluorimetric assay and reactive oxygen species levels as potential biomarkers of genome conditions of dental pulp stem cells (DPSCs) isolated from dog canine teeth. Mesenchymal stem cells were isolated from the dental pulp collected from dog teeth. The results obtained suggest the ideal moment for clinical application of cellular therapy for this type of cell. The cell culture was maintained with Dulbecco's modified Eagle's medium supplemented with 10.00% fetal bovine serum for eight passages. During each passage, cell proliferation, oxidative stress and level of DNA fragmentation were assessed by3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium (MTT) assay, testing 2,7 dichlorodihydro-fluorescein-diacetate and PicoGreen®, respectively. There were important differences among the first three DPSC passages compared to passages 4-8 and a large number of nuclei with some levels of DNA damage (30.00 to 40.00% in initial DPSC passages and > 50.00% in late passages), indicating in vitro DPSC genomic fragility. Within the limitations of this study, the results suggest these relatively simple and inexpensive approaches - comet and DNA fragmentation assays - could help sort stem cells with less DNA damage for use in research or therapies.

RESUMO

Mesenchymal stem cells are a population of somatic cells found in several tissues of an adult organism, including adipose tissue. Reactive oxygen species (ROS) can cause cellular alterations, including mutagenesis and genomic instability and the development of diseases. Thus, it is important to understand ROS-induced damage to cell macromolecules such as DNA, proteins, and lipids. In this study, we investigated oxidative stress rates and viability of adipose tissue-derived mesenchymal stem cells (ADSCs) from the greater omentum of rabbits. Cell cultures were analyzed at different passages (1-5) using the dichlorofluorescein acetate assay for measuring ROS production and cell viability tests. ROS levels were highest at passage 2 and cell viability was highest at passage 4.

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Células-tronco mesenquimais são uma população de células somáticas encontradas em vários tecidos de um organismo adulto, incluindo o tecido adiposo. Espécies reativas de oxigênio (ROS) podem causar alterações celulares, incluindo mutagênese e instabilidade genômica e o desenvolvimento de doenças. Assim, é importante entender o dano induzido pelas EROs às macromoléculas celulares, como DNA, proteínas e lipídios. Neste estudo, investigamos as taxas de estresse oxidativo e viabilidade de células-tronco mesenquimais derivadas do tecido adiposo (ADSCs) a partir do omento maior de coelhos. As culturas celulares foram analisadas em diferentes passagens (1-5) utilizando o ensaio de acetato de diclorofluoresceína para medir a produção de ROS e testes de viabilidade celular. Os níveis de EROs foram mais altos na 2ª passagem e a viabilidade celular foi maior na 4ª passagem.

Assuntos

Animais , Coelhos , Células-Tronco Mesenquimais , Estresse Oxidativo , Sobrevivência Celular , Coelhos , Espécies Reativas de Oxigênio , Terapia Baseada em Transplante de Células e Tecidos

RESUMO

We produced a new chemical compound based on methylxanthines and polyphenols (CCMP) present in the chemical matrix of guaraná (Paullinia cupana), a seed extract with antioxidant properties. After supplementation with the standard extract of resveratrol, a well documented antioxidant found in other plant sources, we investigated whether this resveratrol-enriched compound could improve sperm viability and modulate differentially reactive oxygen species (ROS) and nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy young donors were treated with different concentrations of guaraná extract (0.1, 1, 5 or 10 mg/ml) and cells were frozen at -80°C for 24 h. In addition, the potential protective effects of guaraná treatment on sperm treated with pro-oxidant compound (200 µM hydrogen peroxide, H2O2) were assessed. Samples were also exposed to three concentrations of CCMP before being frozen in liquid nitrogen (-196°C) or in an ultrafreezer (-80°C) for 24 h, and both pre-freezing and post-thaw measurements of viability and oxidative stress were performed. Guaraná supplementation at 10 mg/ml significantly increased post-thaw viability and decreased oxidative metabolism of the sperm. Moreover, selected concentrations of CCMP improved viability and oxidative metabolism in sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by increasing viability and decreasing oxidative stress in post-thaw samples. In summary, these findings suggested that CCMP supplementation acts as a cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used to enhance sperm quality and reproductive success.

Assuntos

Óxido Nítrico/metabolismo , Paullinia/química , Extratos Vegetais/farmacologia , Polifenóis/química , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Xantinas/química , Adulto , Antioxidantes/farmacologia , Crioprotetores/farmacologia , Congelamento , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Análise do Sêmen , Espermatozoides/efeitos dos fármacos , Adulto Jovem

RESUMO

Neuropsychiatric diseases, such as bipolar disorder (BD) and schizophrenia (SCZ), have a very complex pathophysiology. Several current studies describe an association between psychiatric illness and mitochondrial dysfunction and consequent cellular modifications, including lipid, protein, and DNA damage, caused by cellular oxidative stress. Euterpe oleracea (açaí) is a powerful antioxidant fruit. Açaí is an Amazonian palm fruit primarily found in the lowlands of the Amazonian rainforest, particularly in the floodplains of the Amazon River. Given this proposed association, this study analyzed the potential in vitro neuropharmacological effect of Euterpe oleracea (açaí) extract in the modulation of mitochondrial function and oxidative metabolism. SH-SY5Y cells were treated with rotenone to induce mitochondrial complex I dysfunction and before and after we exposed the cells to açaí extract at 5 µg/mL. Treated and untreated cells were then analyzed by spectrophotometric, fluorescent, immunological, and molecular assays. The results showed that açaí extract can potentially increase protein amount and enzyme activity of mitochondrial complex I, mainly through NDUFS7 and NDUFS8 overexpression. Açaí extract was also able to decrease cell reactive oxygen species levels and lipid peroxidation. We thus suggest açaí as a potential candidate for drug development and a possible alternative BD therapy.

Assuntos

Euterpe/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Rotenona/toxicidade , Desacopladores/toxicidade , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Complexo I de Transporte de Elétrons/metabolismo , Frutas , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NADH Desidrogenase/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Espécies Reativas de Oxigênio/metabolismo

RESUMO

The role of superoxide dismutase manganese dependent enzyme (SOD2) in colorectal cancer is presently insufficiently understood. Some studies suggest that high SOD2 levels found in cancer tissues are associated with cancer progression. However, thus far, the role of colorectal cancer superoxide-hydrogen peroxide imbalance has not yet been studied. Thus, in order to address this gap in extant literature, we performed an in vitro analysis using HT-29 colorectal cell line exposed to paraquat, which generates high superoxide levels, and porphyrin, a SOD2 mimic molecule. The effect of these drugs on colorectal cancer cell response to oxaliplatin was evaluated. At 0.1 µM concentration, both drugs exhibited cytotoxic and antiproliferative effect on colorectal cancer cells. However, this effect was more pronounced in cells exposed to paraquat. Paraquat also augmented the oxaliplatin cytotoxic and antiproliferative effects by increasing the number of apoptosis events, thus causing the cell cycle arrest in the S and M/G2 phases. The treatments were also able to differentially modulate genes related to apoptosis, cell proliferation and antioxidant enzyme system. However, the effects were highly variable and the results obtained were inconclusive. Nonetheless, our findings support the hypothesis that imbalance caused by increased hydrogen peroxide levels could be beneficial to cancer cell biology. Therefore, the use of therapeutic strategies to decrease hydrogen peroxide levels mainly during oxaliplatin chemotherapy could be clinically important to the outcomes of colorectal cancer treatment.

Assuntos

Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Peróxido de Hidrogênio/metabolismo , Compostos Organoplatínicos/farmacologia , Superóxido Dismutase/genética , Catalase/genética , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/genética , Células HT29 , Humanos , Oxaliplatina , Paraquat/farmacologia , Porfirinas/farmacologia , Superóxido Dismutase-1/genética

RESUMO

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-1ß, 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.

Assuntos

Anti-Inflamatórios/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Estilbenos/farmacologia , Superóxido Dismutase/genética , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Genótipo , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/enzimologia , Leucócitos Mononucleares/imunologia , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Resveratrol , Sirtuína 1/genética , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo

RESUMO

Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a protective effect against cancer-related fatigue in breast cancer patients undergoing chemotherapy. However, guarana possesses bioactive molecules, such as caffeine and catechin, which may affect the pharmacological properties of antitumor drugs. Therefore, the aim of this study was to evaluate the effects of guarana on breast cancer cell response to 7 chemotherapeutic agents currently used in the treatment of breast cancer. To perform this study, MCF-7 breast cancer cells were cultured under controlled conditions and exposed to 1, 5 and 10 µg/ml guarana concentrations, with and without chemotherapeutics (gemcitabine, vinorelbine, methotrexate, 5-fluorouracil, paclitaxel, doxorubicin and cyclophosphamide). The effect of these treatments on MCF-7 cell viability and proliferation was spectrophotometrically analyzed with the MTT assay. The main results demonstrated an antiproliferative effect of guarana at concentrations of 5 and 10 µg/ml and a significant effect on chemotherapeutic drug action. In general, guarana improved the antiproliferative effect of chemotherapeutic agents, causing a decrease of >40% in cell growth after 72 h of exposure. The results suggested an interaction of guarana with the chemotherapeutic drugs, which requires confirmation by in vivo complementary studies.

RESUMO

INTRODUCTION: Pavonia xanthogloea is traditionally used as an antimicrobial and anti-tumour medicine in Southern Brazilian region. However, investigations about this species are still incipient. HYPOTHESIS TESTED: The study postulated that P. xanthologea specie present some phenolic compound and present some biological properties as anti-oxidant and cytoprotective effect against oxidative stress. MATERIALS AND METHODS: The content of eight phenolic molecules in the crude ethanolic extract of the aerial part of P. xanthogloea and its five fractions (hexane, dichloromethane, ethyl-acetate, n-butanol, and water) was determined by heterotrophic plate count method. The anti-oxidant capacity of the extract and the fractions was determined by 1,1-diphenyl-2-picryl-hydrazyl assay. The potential anti-oxidant and cytoprotective effect was also analyzed in human lymphocyte culture treated with extract/fractions at different concentrations with and without oxidative stress generated by hydrogen peroxide (H2O2) and sodium nitroprusside (SNP) exposition. RESULTS: Tiliroside was the molecule detected in all extract. Water and ethyl-acetate fractions showed the highest radical-scavenging activity. The crude extract, hexane, water, and n-butanol reversed the higher reactive oxygen specie levels generated by H2O2 and SNP to levels similar to those observed in the control group. In addition, crude extract, hexane, ethyl-acetate and n-butanol did not caused cytotoxicity, whereas water fraction was cytotoxic at higher concentration tested here (300 µg/mL). The cytotoxicity reversion caused by SNP exposition was concentration-dependent of the extract and fractions. However, dichloromethane fraction increased cell mortality in all concentrations investigated and was not able to decrease cell death in the lymphocytes exposed to SNP. CONCLUSION: The results suggest potential medicine use of this species.