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1.
Food Chem Toxicol ; 53: 310-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23261678

RESUMO

Breast cancer constitutes a major health problem for women worldwide. However, its incidence varies between populations and geographical locations. These variations could be diet-related, since there are several carcinogenic compounds in the modern diet, while natural products contain various anti-cancer elements. Several lines of evidence indicate that, in addition to their clear preventive effect, these compounds could also be used as therapeutic agents. In the present report we have shown that oleuropein, a pharmacologically safe natural product of olive leaf, has potent anti-breast cancer properties. Indeed, oleuropein exhibits specific cytotoxicity against breast cancer cells, with higher effect on the basal-like MDA-MB-231 cells than on the luminal MCF-7 cells. This effect is mediated through the induction of apoptosis via the mitochondrial pathway. Moreover, oleuropein inhibits cell proliferation by delaying the cell cycle at S phase and up-regulated the cyclin-dependent inhibitor p21. Furthermore, oleuropein inhibited the anti-apoptosis and pro-proliferation protein NF-κB and its main oncogenic target cyclin D1. This inhibition could explain the great effect of oleuropein on cell proliferation and cell death of breast cancer cells. Therefore, oleuropein warrants further investigations to prove its utility in preventing/treating breast cancer, especially the less-responsive basal-like type.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Óleos de Plantas/farmacologia , Piranos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Eletroforese em Gel de Poliacrilamida , Feminino , Citometria de Fluxo , Humanos , Glucosídeos Iridoides , Iridoides , Células MCF-7 , Mitocôndrias/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Azeite de Oliva , Receptores de Estrogênio/metabolismo , Regulação para Cima
2.
Oxid Med Cell Longev ; 2012: 194829, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22888396

RESUMO

Reactive oxygen species (ROS) are cytotoxic agents that lead to significant oxidative damage. Bisphenol A (BPA) is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells. Due to limited information concerning the effect of BPA on liver, this study investigates whether BPA causes hepatotoxicity by induction of oxidative stress in liver. Rats were divided into five groups: The first four groups, BPA (0.1, 1, 10, 50 mg/kg/day) were administrated orally to rats for four weeks. The fifth group was taken water with vehicle. The final body weights in the 0.1 mg group showed a significant decrease compared to control group. Significant decreased levels of reduced glutathione, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase activity were found in the 50 mg BPA group compared to control groups. High dose of BPA (50 mg/kg) significantly increased the biochemical levels of ALT, ALP and total bilirubin. BPA effect on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decrease compared to control. Data from this study demonstrate that BPA generate ROS and reduce the antioxidant gene expression that causes hepatotoxicity.


Assuntos
Hepatopatias/patologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Animais , Compostos Benzidrílicos , Bilirrubina/metabolismo , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Hepatopatias/enzimologia , Hepatopatias/genética , Masculino , Nitrosação/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar
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