Higher concentrations of palmitate on PC3 cells and palmitate and insulin on PNT1A cells stimulate cellular activities that could favor cancer progression. Metformin inhibited most of these stimuli, showing the efficacy of this drug for cancer adjuvant therapy in obese patients (a group at increased risk for the development of prostrate cancer).
Recent studies have been trying to find out how diet and metabolic changes such as dyslipidaemia, hyperglycaemia, and hyperinsulinaemia can stimulate cancer progression. This investigation aimed to evaluate the effect of high concentrations of fatty acids and/or glucose in tumour prostate cells, focusing on the proliferation/migration profile and oxidative stress. PC3 cells were treated with high concentration of saturated fatty acid (palmitate, 100 mM), glucose (220 mg/dL), or both for 24 or 48 h. Results demonstrated that PC3 cells showed a significant increase in proliferation after 48 h of treatment with glucose and palmitateþglucose. Cell proliferation was associated with reduced levels of AMPK phosphorylation in glucose group at 24 and 48 h of treatment, while palmitate group presented this result only after 48 h of treatment. Also, there was a significant increase in cell migration between time 0 and 48 h after all treatments, except in the control. Catalase activity was increased by palmitate in the beginning of treatment, while glucose presented a later effect. Also, nitrite production was increased by glucose only after 48 h, and the total antioxidant activity was enhanced by palmitate in the initial hours. Thus, we conclude that the high concentration of the saturated fatty acid palmitate and glucose in vitro influences PC3 cells and stimulates cellular activities related to carcinogenesis such as cell proliferation, migration, and oxidative stress in different ways. Palmitate presents a rapid and initial effect, while a glucose environment stimulates cells later on, maintaining high levels of cell proliferation.
Background and Aim Maytenus ilicifolia has analgesic, healing, antioxidant and anti-inflammatory properties. This study evaluated effect of the hydroalcoholic extract of M. ilicifolia leaves on skin wound repair. Experimental procedure Wounds were induced on mice and treated with the extract. The treatment was performed daily, until day 7 after wound induction. Wound closure was measured and the features of the repaired tissue were investigated, including mast cell quantification, neutrophil and macrophage activities, collagen deposition, angiogenesis, and pro-metalloproteases and metalloproteases 2 and 9 activity (pro-MMPs and MMPs). Results and conclusion The M. ilicifolia extract accelerated the closure of wounds. The extract at a concentration of 4% was found to be effective, presenting anti-inflammatory effects and hemoglobin increased, along with increased soluble, total and type III collagens in the wound. In addition, there was an increase in pro-MMP9 and MMP9 activity after day 7th of treatment. The phenolic compounds and tannins present in this plant could be associated with the anti-inflammatory and healing activities observed in this study. Therefore, the ability to modulate essential parameters for accelerated and adequate healing as shown here suggests that the use of standardised extracts of M. ilicifolia and its fractions enriched in polyphenols may represent a therapeutic strategy for the treatment of wounds.
Atualmente tem se discutido uma possível relação entre obesidade e câncer de próstata. No entanto, a obesidade está associada a desordens multifatoriais (hiperglicemia, hiperinsulinemia, dislipidemia, inflamação) e avaliar o impacto delas em células normais e tumorais é de grande relevância para a elaboração de estratégias terapêuticas. A metformina é uma droga antidiabética que apresenta efeitos antiproliferativos e tem sido apontada como tratamento para o câncer. Entretanto, sua eficiência em condições de intenso estímulo proliferativo ainda é desconhecida. Assim, este estudo objetivou analisar o efeito de altas concentrações de ácido graxo e/ou insulina, com ou sem metformina,em células normais e tumorais de próstata, com ênfase no perfil de proliferação e migração destas células. Foram utilizadas duas linhagens de células epiteliais humanas de próstata, sendo elas normais (PNT1A) e tumorais (PC3). Estas células foram tratadas com altas concentrações de ácido graxo saturado (100 gM palmitato, HF), e/ou insulina (50gU), na presença ou ausência de metformina (100 gM), por 24hrs ou 48hrs. Posteriormente, estas células foram submetidas às análises de apoptose, viabilidade/proliferação celular (MTT), migração e imunofluorescência para vimentina. Os resultados mostram que, de maneira geral, os tratamentos nas concentrações usadas não causaram morte celular nas células estudadas. O MTT revelou que as células PNT1A e PC3 proliferaram em maior quantidade quando tratadas com altas concentrações de ácido graxos (HF) e de insulina (HI) após as primeiras horas de tratamento. O mesmo resultado não foi observado para o grupo HFI. A metformina por si só estimulou a proliferação celular, mas em associação à HF foi capaz de reduzi-la em ambas as linhagens. Contudo, ela não inibiu a proliferação celular desencadeada por HI nas células normais.As análises de migração mostraram que PNT1A foram estimuladas a migrar para todos os tratamentos, enquanto PC3 foi influenciada somente por HF. A metformina inibiu a migração estimulada por todos eles. Em paralelo à migração, foi observado que os tratamentos HF e HI para PNT1A e HF para PC3 estimularam a maior expressão de vimentina, demonstrando maior transição epitélio mesenquima nessas células, e, consequentemente, estimulando a migração celular. A metformina inibiu a expressão de vimentina estimulada pelos meios tanto nas células normais como nas tumorais. Assim, conclui-se que as altas concentrações de ácido graxo saturado e insulina interferem nas células prostáticas estimulando atividades celulares que sabidamente influenciam na carcinogênese, tais como proliferação e migração celular. A metformina foi capaz de reverter boa parte das alterações estimuladas por esses meios, se mostrando uma boa ferramenta no controle da proliferação e migração celular em situações de hiperlipidemia e hiperinsulinemia. Assim, o potencial dessa droga para a terapia de pacientes obesos que sabidamente apresentam maior risco para câncer de próstata deverá ser investigado.
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