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1.
Nutrients ; 13(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445015

RESUMO

Oxidative stress is involved in the metabolic dysregulation of type 2 diabetes (DM2). Acrocomia aculeata (Aa) fruit pulp has been described for the treatment of several diseases, and recently we have proved that its leaves have phenolic compounds with a marked antioxidant effect. We aimed to assess whether they can improve metabolic, redox and vascular functions in DM2. Control Wistar (W-Ctrl) and non-obese type 2 diabetic Goto-Kakizaki (GK-Ctrl) rats were treated for 30 days with 200 mg.kg-1 aqueous extract of Aa (EA-Aa) (Wistar, W-EA-Aa/GK, GK-EA-Aa). EA-Aa was able to reduce fasting glycaemia and triglycerides of GK-EA-Aa by improving proteins related to glucose and lipid metabolism, such as GLUT-4, PPARγ, AMPK, and IR, when compared to GK-Ctrl. It also improved viability of 3T3-L1 pre-adipocytes exposed by H2O2. EA-Aa also increased the levels of catalase in the aorta and kidney, reduced oxidative stress and increased relaxation of the aorta in GK-treated rats in relation to GK-Ctrl, in addition to the protective effect against oxidative stress in HMVec-D cells. We proved the direct antioxidant potential of the chemical compounds of EA-Aa, the increase in antioxidant defences in a tissue-specific manner and hypoglycaemic properties, improving vascular function in type 2 diabetes. EA-Aa and its constituents may have a therapeutic potential for the treatment of DM2 complications.


Assuntos
Antioxidantes/farmacologia , Aorta/efeitos dos fármacos , Arecaceae , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vasodilatação/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Antioxidantes/isolamento & purificação , Aorta/metabolismo , Aorta/fisiopatologia , Arecaceae/química , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Frutas , Humanos , Hipoglicemiantes/isolamento & purificação , Lipídeos/sangue , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Ratos Wistar
2.
Nutr Cancer ; 68(2): 250-66, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26943884

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary liver tumor (PLT), with cholangiocarcinoma (CC) being the second most frequent. Glucose transporter 1 (GLUT-1) expression is increased in PLTs and therefore it is suggested as a therapeutic target. Flavonoids, like quercetin, are GLUT-1 competitive inhibitors and may be considered as potential therapeutic agents for PLTs. The objective of this study was evaluation of quercetin anticancer activity in three human HCC cell lines (HepG2, HuH7, and Hep3B2.1-7) and in a human CC cell line (TFK-1). The possible synergistic effect between quercetin and sorafenib, a nonspecific multikinase inhibitor used in clinical practice in patients with advanced HCC, was also evaluated. It was found that in all the cell lines, quercetin induced inhibition of the metabolic activity and cell death by apoptosis, followed by increase in BAX/BCL-2 ratio. Treatment with quercetin caused DNA damage in HepG2, Hep3B2.1-7, and TFK-1 cell lines. The effect of quercetin appears to be independent of P53. Incubation with quercetin induced an increase in GLUT-1 membrane expression and a consequent reduction in the cytoplasmic fraction, observed as a decrease in (18)F-FDG uptake, indicating a GLUT-1 competitive inhibition. The occurrence of synergy when sorafenib and quercetin were added simultaneously to HCC cell lines was noticed. Thus, the use of quercetin seems to be a promising approach for PLTs through GLUT-1 competitive inhibition.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Quercetina/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Fluordesoxiglucose F18/farmacocinética , Transportador de Glucose Tipo 1/metabolismo , Células Hep G2/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quercetina/administração & dosagem , Sorafenibe , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
Cancer Metastasis Rev ; 34(4): 563-73, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25579236

RESUMO

Retinoblastoma is a tumor that mainly affects children under 5 years, all over the world. The origin of these tumors is related with mutations in the RB1 gene, which may result from genetic alterations in cells of the germ line or in retinal somatic cells. In developing countries, the number of retinoblastoma-related deaths is higher due to less access to treatment, unlike what happens in developed countries where survival rates are higher. However, treatments such as chemotherapy and radiotherapy, although quite effective in treating this type of cancer, do not avoid high indices of mortality due to secondary malignances which are quite frequent in these patients. Additionally, treatments such as cryotherapy, thermotherapy, thermochemotherapy, or brachytherapy represent other options for retinoblastoma. When all these approaches fail, enucleation is the last option. Photodynamic therapy might be considered as an alternative, particularly because of its non-mutagenic character. Photodynamic therapy is a treatment modality based on the administration of photosensitizing molecules that only upon irradiation of the tumor with a light source of appropriate wavelength are activated, triggering its antitumor action. This activity may be not only due to direct damage to tumor cells but also due to damage caused to the blood vessels responsible for the vascular supply of the tumor. Over the past decades, several in vitro and in vivo studies were conducted to assess the effectiveness of photodynamic therapy in the treatment of retinoblastoma, and very promising results were achieved.


Assuntos
Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Retinoblastoma/terapia , Pré-Escolar , Humanos , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Proteína do Retinoblastoma/genética
4.
Nutr Cancer ; 63(4): 479-94, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21541902

RESUMO

Vitamins are essential nutrients for human metabolism, playing an important role as coenzymes or enzymes in many vital processes for the normal functioning of the body. In recent years, it has become apparent that vitamins are crucial in health and human disease, due to several studies that studied this relationship. Currently, it is known that vitamins can have an important role in the prevention and treatment of cancer, but until now no conclusive results were obtained. In this review, we will present the work and more relevant conclusions obtained in recent years of investigation about the relationship between vitamins and cancer, namely vitamin A, vitamin B complex, vitamin C, vitamin D, vitamin E, and vitamin K.


Assuntos
Quimioprevenção , Suplementos Nutricionais , Neoplasias/prevenção & controle , Vitaminas/farmacologia , Ácido Ascórbico/farmacologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina A/farmacologia , Complexo Vitamínico B/farmacologia , Vitamina D/farmacologia , Vitamina E/farmacologia , Vitamina K/farmacologia
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