Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros

Métodos Terapêuticos e Terapias MTCI
Base de dados
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
PLoS One ; 10(8): e0135704, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26285134

RESUMO

Tumor cells adapt via metabolic reprogramming to meet elevated energy demands due to continuous proliferation, for example by switching to alternative energy sources. Nutrients such as glucose, fatty acids, ketone bodies and amino acids may be utilized as preferred substrates to fulfill increased energy requirements. In this study we investigated the metabolic characteristics of benign and cancer cells of the prostate with respect to their utilization of medium chain (MCTs) and long chain triglycerides (LCTs) under standard and glucose-starved culture conditions by assessing cell viability, glycolytic activity, mitochondrial respiration, the expression of genes encoding key metabolic enzymes as well as mitochondrial mass and mtDNA content. We report that BE prostate cells (RWPE-1) have a higher competence to utilize fatty acids as energy source than PCa cells (LNCaP, ABL, PC3) as shown not only by increased cell viability upon fatty acid supplementation but also by an increased ß-oxidation of fatty acids, although the base-line respiration was 2-fold higher in prostate cancer cells. Moreover, BE RWPE-1 cells were found to compensate for glucose starvation in the presence of fatty acids. Of notice, these findings were confirmed in vivo by showing that PCa tissue has a lower capacity in oxidizing fatty acids than benign prostate. Collectively, these metabolic differences between benign and prostate cancer cells and especially their differential utilization of fatty acids could be exploited to establish novel diagnostic and therapeutic strategies.


Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Próstata/citologia , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Linhagem Celular Tumoral , Respiração Celular , Sobrevivência Celular , DNA Mitocondrial/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Ácidos Graxos/química , Dosagem de Genes , Genoma Mitocondrial/genética , Glicólise , Humanos , Corpos Cetônicos/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Tamanho Mitocondrial , Fosforilação Oxidativa , Próstata/metabolismo , Triglicerídeos/metabolismo
2.
Nutrients ; 6(10): 4491-519, 2014 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-25338271

RESUMO

Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Diabetes Mellitus Tipo 2/dietoterapia , Suplementos Nutricionais , Osteoporose/dietoterapia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Cálcio da Dieta/administração & dosagem , Cálcio da Dieta/farmacologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Ácidos Graxos/administração & dosagem , Ácidos Graxos/farmacologia , Humanos , Masculino , Osteoporose/induzido quimicamente , Fitoestrógenos/administração & dosagem , Fitoestrógenos/farmacologia , Selênio/administração & dosagem , Selênio/farmacologia , Resultado do Tratamento , Vitamina D/administração & dosagem , Vitamina D/farmacologia , Vitamina E/administração & dosagem , Vitamina E/farmacologia
3.
Phytomedicine ; 20(14): 1306-14, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23972793

RESUMO

This study aimed to investigate the mechanisms underlying the anti-proliferative effects of the ethanolic Cimicifuga racemosa extract BNO-1055 on prostate cells and evaluate its therapeutic potential. BNO-1055 dose-dependently attenuated cellular uptake and incorporation of thymidine and BrdU and significantly inhibited cell growth after long-time exposure. Similar results were obtained using saponin-enriched sub-fractions of BNO-1055. These inhibitory effects of BNO-1055 could be mimicked using pharmacological inhibitors and isoform-specific siRNAs targeting the equilibrative nucleoside transporters ENT1 and ENT2. Moreover, BNO-1055 attenuated the uptake of clinically relevant nucleoside analogs, e.g. the anti-cancer drugs gemcitabine and fludarabine. Consistent with inhibition of the salvage nucleoside uptake pathway BNO-1055 potentiated the cytotoxicity of the de novo nucleotide synthesis inhibitor 5-FU without significantly altering its uptake. Collectively, these data show for the first time that the anti-proliferative effects of BNO-1055 result from hindered nucleoside uptake due to impaired ENT activity and demonstrate the potential therapeutic use of BNO-1055 for modulation of nucleoside transport.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Proteínas de Transporte de Nucleosídeo Equilibrativas/metabolismo , Nucleosídeos/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Próstata/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/farmacologia , Bromodesoxiuridina/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Cimicifuga , Desoxicitidina/análogos & derivados , Desoxicitidina/metabolismo , Relação Dose-Resposta a Droga , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Masculino , Extratos Vegetais/farmacologia , Neoplasias da Próstata/metabolismo , RNA Interferente Pequeno/farmacologia , Saponinas/farmacologia , Saponinas/uso terapêutico , Timidina/metabolismo , Vidarabina/análogos & derivados , Vidarabina/metabolismo , Gencitabina
4.
Cancer Immunol Immunother ; 55(11): 1374-83, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16485125

RESUMO

We evaluated tumor cell growth modulation by bee venom secretory phospholipase A2 (bv-sPLA2) and phosphatidylinositol-(3,4)-bisphosphate as well as potential cooperative effects. In addition, the immunomodulatory impact of tumor cell treatment was examined by monitoring changes in phenotype and function of monocyte-derived dendritic cells (moDCs) cocultured with pretreated tumor cells. Bv-sPLA2 or phosphatidylinositol-(3,4)-bisphosphate alone displayed moderate effects on the proliferation of A498 renal cell carcinoma cells, T-47D breast cancer cells, DU145 prostate cancer cells and BEAS-2B transformed lung cells. However, when bv-sPLA2 was coadministered with phosphatidylinositol-(3,4)-bisphosphate a potent inhibition of [3H] thymidine incorporation into all tested cell lines occurred. This inhibition was due to massive cell lysis that reduced the number of cells with proliferative capacity. Importantly, tumor cell lysates generated with bv-sPLA2 plus phosphatidylinositol-(3,4)-bisphosphate induced maturation of human moDCs demonstrated by enhanced expression of CD83 and improved stimulation in allogeneic mixed leukocyte reactions. Our data demonstrate that bv-sPLA2 and phosphatidylinositol-(3,4)-bisphosphate synergistically generate tumor lysates which enhance the maturation of immunostimulatory human monocyte-derived dendritic cells. Such tumor lysates which represent complex mixtures of tumor antigens and simultaneously display potent adjuvant properties meet all requirements of a tumor vaccine.


Assuntos
Neoplasias/tratamento farmacológico , Fosfatos de Fosfatidilinositol/química , Fosfolipases A/metabolismo , Animais , Venenos de Abelha/metabolismo , Vacinas Anticâncer/química , Linhagem Celular Tumoral , Proliferação de Células , Células Dendríticas/citologia , Fosfolipases A2 do Grupo II , Caranguejos Ferradura , Humanos , Leucócitos/citologia , Monócitos/citologia , Monócitos/metabolismo , Neoplasias/metabolismo , Fosfolipases A2 , Linfócitos T/citologia
5.
Exp Hematol ; 33(2): 144-50, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15676206

RESUMO

OBJECTIVE: Dendritic cells (DCs), also referred to as the sentinels of the immune system, induce and coordinate important functions of immune surveillance. Prostaglandin E2 (PGE2), a member of the eicosanoid family of arachidonic acid derivatives, is widely used to enhance the TNF-alpha-driven maturation of human monocyte-derived DCs (moDCs) both in basic research and in clinical settings. However, PGE2 is known to rapidly undergo nonenzymatic dehydration to produce PGA2, a member of the cyclopentenone PGs, which have been implicated in anti-inflammatory processes. METHODS: In a side-by-side analysis we therefore compared the influence of PGE2 and PGA2 on the TNF-alpha-induced maturation of human moDCs. Phenotypic changes, migratory responses towards MIP-3beta, and T-cell responses induced by the differentially matured moDCs were assessed. RESULTS: We found that PGA2 is nearly as potent as PGE2 in costimulating the TNF-alpha-induced phenotypic maturation of human moDCs. Both PGE2 and PGA2 further enhanced the migratory and T-cell-stimulatory capacity of TNF-alpha-treated moDCs. Maturation of moDCs with either PGE2 or PGA2 resulted in enhanced IFN-gamma, TNF-alpha, and IL-5 production and repressed IL-10 production in allogeneic mixed leukocyte cultures. PGE2 was always more potent than PGA2. CONCLUSIONS: Our data suggest that some of the effects attributed to PGE2 may in fact be mediated by its degradation product PGA2. This work also demonstrates that cyclopentenone PGs may have pro-inflammatory properties and that both PGE2 and PGA2 can contribute to the development of Th1-type immune responses.


Assuntos
Células Dendríticas/citologia , Monócitos/citologia , Prostaglandinas A/farmacologia , Adjuvantes Imunológicos/farmacologia , Células Cultivadas , Quimiotaxia de Leucócito , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Dinoprostona/farmacologia , Citometria de Fluxo , Humanos , Monócitos/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA