RESUMO
We investigated the effects of the drug 14-keto-stypodiol diacetate (SDA) extracted from the seaweed product Stypopodium flabelliforme, in inhibiting the cell growth and tumor invasive behavior of DU-145 human prostate cells. In addition, the molecular action of the drug on microtubule assembly was analyzed. The effects of this diterpenoid drug in cell proliferation of DU-145 tumor cells in culture revealed that SDA at concentrations of 5 microM decreased cell growth by 14%, while at 45 microM a 61% decrease was found, as compared with control cells incubated with the solvent but in the absence of the drug. To study their effects on the cell cycle, DU-145 cells were incubated with increasing concentrations of SDA and the distribution of cell-cycle stages was analyzed by flow cytometry. Interestingly, the data showed that 14-keto-stypodiol diacetate dramatically increased the proportion of cells in the G2/M phases, and decreased the number of cells at the S phase of mitosis, as compared with appropriate controls. Studies on their action on the in vitro assembly of microtubules using purified brain tubulin, showed that SDA delayed the lag period associated to nucleation events during assembly, and decreased significantly the extent of polymerization. The studies suggest that this novel derivative from a marine natural product induces mitotic arrest of tumor cells, an effect that could be associated to alterations in the normal microtubule assembly process. On the other hand, a salient feature of this compound is that it affected protease secretion and the in vitro invasive capacity, both properties of cells from metastases. The secretion of plasminogen activator (u-PA) and the capacity of DU-145 cells to migrate through a Matrigel-coated membrane were significantly inhibited in the presence of micromolar concentrations of SDA. These results provide new keys to analyze the functional relationships between protease secretion, invasive behavior of tumor cells and the microtubule network.
Assuntos
Divisão Celular/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Neoplasias da Próstata/patologia , Quinonas/farmacologia , Citometria de Fluxo , Humanos , L-Lactato Desidrogenase/metabolismo , Masculino , Proteínas dos Microtúbulos/isolamento & purificação , Microtúbulos/metabolismo , Invasividade Neoplásica , Ativadores de Plasminogênio/antagonistas & inibidores , Ativadores de Plasminogênio/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Alga Marinha , Células Tumorais CultivadasRESUMO
BACKGROUND: 25-hydroxyvitamin D has a longer half life and its serum levels have less daily variations than calcitriol. Thus, its measurement is a better indicator of vitamin D status. AIM: To measure 25-hydroxyvitamin D levels in normal subjects during summer and winter. PATIENTS AND METHODS: Vitamin D was measured using a competitive protein binding radioassay in 61 subjects (27 male) aged 21 to 57 years old, during July and August (winter) and February and March of the next year (summer). RESULTS: 25-hydroxyvitamin levels were 28.8 +/- 1.5 and 30.9 +/- 2.3 ng/ml during winter and summer respectively. No differences were found between men and women. Ninety five percent confidence levels were between 13 and 50 ng/ml. Levels in one patient with malabsorption were 9.3 ng/ml, in 2 patients with hypophosphatemic osteomalacia were 2.1 and 9.3 ng/ml, in 12 patients with alcoholic cirrhosis were 16.4 +/- 1.3 ng/ml, in 4 patients with primary osteoporosis were 23.3 +/- 0.7 and in three patients receiving vitamin D were 334 +/- 33.2 ng/ml. CONCLUSIONS: Normal levels of 25-hydroxyvitamin D range from 13 to 50 ng/ml in normal adults, there are no differences between men and women and seasonal variations are minimal.
Assuntos
Hidroxicolecalciferóis/sangue , Estações do Ano , Adulto , Feminino , Humanos , Cirrose Hepática Alcoólica/sangue , Síndromes de Malabsorção/sangue , Masculino , Pessoa de Meia-Idade , Osteomalacia/sangue , Osteoporose/sangue , Ensaio Radioligante , Valores de Referência , Fatores SexuaisRESUMO
Fluoxetine, a serotonin re-uptake inhibitor with antidepressive and appetite reduction effects, could improve insulin sensitivity. The aim of this work was to assess this effect of fluoxetine in obese subjects. We studied 12 subjects with a body mass index over 30, with a normal oral glucose tolerance test and not subjected to dietary restrictions. Insulin sensitivity using Bergman's minimal model, sex hormone binding globulin (SHBG) and insulin like growth factor binding protein 1 (BP 1) were evaluated before and after three weeks of treatment with 60 mg OD of fluoxetine. During treatment, subjects lost a mean of 1.9 kg. When compared with basal values, insulin sensitivity index (S1) improved significantly at the end of treatment (1.71 +/- 0.44 and 2.72 +/- 0.63 respectively), SHBG increased (28.9 +/- 5.1 and 18.2 +/- 3.4 nM/ml respectively) and BP 1 did not change (2.8 +/- 0.9 and 1.5 +/- 0.3 ng/ml respectively). The changes in insulin sensitivity did not correlate with weight changes (r = 0.4 NS). Weight or insulin sensitivity changes did not correlate with initial degree of insulin resistance. We conclude that the improvement in insulin sensitivity elicited by Fluoxetine is not related to weight changes and may be useful in the treatment of insulin resistant obese subjects.
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Fluoxetina/uso terapêutico , Resistência à Insulina/fisiologia , Obesidade/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/metabolismo , Fluoxetina/metabolismo , Teste de Tolerância a Glucose , Humanos , Masculino , Obesidade/metabolismo , Redução de Peso/efeitos dos fármacosRESUMO
Mammary gland growth and differentiation are largely dependent on a complex and interrelated action of many different hormones which makes the mammary tissue a very suitable one for the study of heterologous hormonal regulation. This type of control is analyzed by two different approaches: 1. The participation of estradiol in prolactin action during lactation, and 2. The role of glucocorticoids and thyroid hormones in the control of functional activity of rat mammary gland beta-adrenergic receptors.