RESUMO
Genistein, a major isoflavone found in soybeans, exhibits anticarcinogenic properties. The inhibitory effect of genistein on cell proliferation is associated with G2/M cell cycle arrest and inhibition of cdc2 activities. Here we assessed the role of PTEN in regulation of genistein-mediated G2/M cell cycle arrest in the gastric cancer cell lines (SGC-7901 and BGC-823). After 24 h following treatment, genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by genistein in SGC-7901 and BGC-823 cells is associated with increased phospho-cdc2 (Tyr15) and decreased cdc2 protein. Genistein treatment increased Wee1 levels and decreased phospho-Wee1 (Ser 642). Moreover, genistein substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in genistein-treated cells increased phospho-Wee1 (Ser642), whereas decreased phospho-Cdc2 (Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by genistein involved upregulation of PTEN.
Assuntos
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Genisteína/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias Gástricas/metabolismo , Proteína Quinase CDC2 , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina B/genética , Ciclina B/metabolismo , Quinases Ciclina-Dependentes , Regulação para Baixo , Fase G2/efeitos dos fármacos , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , PTEN Fosfo-Hidrolase/genética , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: To explore the expression of uncoupling protein-2 mRNA in brown adipose tissue, white adipose tissue and skeletal muscle of diet-induced obesity-resistant (DIO-R) rats. METHODS: Fifty male Sprague-Dawley (SD) rats were randomly divided into a control group and a high-fat group and fed with basic diet and high-fat diet respectively for 13 weeks. DIO-R and DIO rats were selected according to their body weight. The change of body weight and the intake of total calorie were observed. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of UCP2 mRNA in rat. RESULTS: Body weight and total calorie intake in DIO-R rats (425.1 +/- 27.1) g, (31,693 +/- 946) kJ were significantly lower than those in DIO rats (489.7 +/- 20.5) g, (34,363 +/- 1465) kJ. The peak area of UCP2 mRNA in white adipose tissue in DIO-R rats was 352 +/- 30 and in DIO rats was 101 +/- 12. The peak areas of UCP2 mRNA in skeletal muscle in DIO-R and DIO rats were 130 +/- 15 and 170 +/- 12, respectively. The peak areas of UCP2 mRNA in brown adipose tissue of DIO and DIO-R rats were 124 +/- 14 and 147 +/- 19, respectively. CONCLUSION: The expression of UCP2 mRNA in white adipose tissue of DIO-R rats increased significantly. These results suggest that obesity-resistance was associated with a tissue-specific increase in UCP2 expression.
