RESUMO
The aim of this study was to determine whether enhanced expression of N-myc in a neuroblastoma cell line affects the balance of plasminogen activator/plasminogen activator inhibitor (PA/PAI), a shift towards proteolysis having been observed in other malignant tissues. Two transfected neuroblastoma cell lines with (WAC2 cells) or without (SH-EP007 cells) enhanced expression of the N-myc oncogene were examined by zymography and RNA extraction to determine UPA and PAI enzyme activity and uPA RNA and PAI RNA expression, respectively. The effect of genistein, an inhibitor of tyrosine protein kinase, on uPA/PAI was also investigated. Both the uPA/PAI-1 ratio at mRNA level and the PA/PAI ratio at protein activity level were higher in the more malignant, WAC2 cell line. Genistein attenuated uPA activity and stimulated PAI activity in both cell lines, leading to a decrease in the PA/PAI ratio. This effect was more pronounced in the more malignant, WAC2 cell line.
Assuntos
Inibidores Enzimáticos/farmacologia , Genes myc , Genisteína/farmacologia , Proteínas de Neoplasias/metabolismo , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Divisão Celular/efeitos dos fármacos , Expressão Gênica , Humanos , RNA Mensageiro/metabolismo , Células Tumorais CultivadasRESUMO
Proliferation of both mouse and human breast cancer cells was inhibited by chlorpheniramine (CPA) in a dose-response manner. At the beginning of the exponential phase of growth (two days after seeding), 250 microM CPA was able to reduce cell proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7 cultures). The antiproliferative effect of CPA was also tested on a poorly-differentiated and hormone-insensitive human breast cancer cell line (MDA-MB231) and on a highly proliferative human colon cancer cell line (clone 3). CPA was cytotoxic for MDA-MB231 cells at concentrations higher than 50 microM, and it was also cytotoxic for the colon cancer cell clone 3 at 250 microM CPA. Nevertheless, colon cancer cells were slightly stimulated at CPA concentrations less than 100 microM. CPA reduced (by 50-70%) the ornithine decarboxylase induction occurring early after culture seeding of experimental mammary tumors (Ehrlich carcinoma cells) and human breast cancer cells (MCF-7). The presented data suggest that in addition to ODC inhibition, CPA presents other still unknown cytotoxic effects.
Assuntos
Neoplasias da Mama/enzimologia , Clorfeniramina/farmacologia , Ornitina Descarboxilase/biossíntese , Animais , Neoplasias da Mama/patologia , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/enzimologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Mamárias Experimentais/enzimologia , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Camundongos , Ornitina Descarboxilase/genética , RNA Mensageiro/genética , Células Tumorais CultivadasRESUMO
2 mM Ascorbic acid has a potent cytotoxic effect on neuroblastoma, osteosarcoma, retinoblastoma, and rhabdomyosarcoma cells cultured in vitro. At a lower concentration (0.2 mM), ascorbic acid remains highly cytotoxic for neuroblastoma, osteosarcoma and retinoblastoma cells, but it has a stimulatory effect on the growth of rhabdomyosarcoma cells.
