RESUMO
Polyphenols extracted from many plants have shown antiproliferative and antitumor activities in a wide range of carcinogenesis models. The antiproliferative effects of polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) were investigated on the androgen-insensitive DU145 human prostatic carcinoma cell line. A F3 fraction purified from leaf extract inhibited the DU145 cell proliferation more than 30-fold compared to the crude extract. By flow cytometric analysis, the polyphenol fraction was demonstrated to induce G0/G1 cell growth arrest and cell apoptosis. This apoptosis was evidenced by caspase 3 stimulation in F3-treated cells as compared to crude extract treated cells. The acid phosphatase activity of lysosomes was strongly activated in the lysosomal fraction of the F3-treated DU145 cells. This lysosomal activation, together with the appearance of autophagic vacuoles, suggests that "type 2 physiological cell death" was also involved in this antiproliferative effect. HPLC analysis of this F3 fraction showed 18 different subfractions. Among these subfractions, F3-3, F3-7 and F3-13 strongly inhibited DU145 cell proliferation in a dose-dependent manner. However, the nature of these polyphenols remains unknown since only one (Isoquercitrin) of the tested pure polyphenols co-migrated with F3-13. Since lysosomotropic drugs are considered as possible regulators of lysosome activity, aroeira polyphenols could target lysosomes of prostatic cancer cells to induce autophagic cell death.
Assuntos
Anacardiaceae/química , Apoptose/efeitos dos fármacos , Fenóis/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Citometria de Fluxo , Humanos , Concentração Inibidora 50 , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/patologia , Fenóis/isolamento & purificação , Neoplasias da Próstata/patologiaRESUMO
Zinc ions have been reported to stabilize cellular membranes, protecting the gastric mucosa against a wide variety of ulcerative agents. The treatment with zinc sulfate intragastrically administered as one dose (20 mg/Kg body weight) daily for 30 consecutive days did not modify the normal aspect of rat gastric mucosa as observed by electron sanning microscopy. Furthermore, the X-ray microanalysis of the lysosome content performed on different gastric mucosa cells did not show the zinc element. These results suggest that zinc ion is a relatively nontoxic element for the rat gastric mucosa