RESUMO
The PI3K-Akt-mTOR, Wnt/ß-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/ß-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, ß-catenin, Gsk3ß, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/ß catenin signaling pathways and induction of apoptosis pathway.
Assuntos
Anticarcinógenos/farmacologia , Mel , Extratos Vegetais/farmacologia , Serina-Treonina Quinases TOR/genética , Via de Sinalização Wnt/efeitos dos fármacos , Zingiber officinale , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Proteínas de Transporte/genética , Caspase 3/genética , Sobrevivência Celular/efeitos dos fármacos , Quimioprevenção , Ciclina D1/genética , Citocromos c/genética , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/genética , Glicogênio Sintase Quinase 3 beta , Células HT29 , Humanos , Concentração Inibidora 50 , Melaleuca , Proteínas Proto-Oncogênicas c-akt/genética , Proteína Companheira de mTOR Insensível à Rapamicina , Proteína Regulatória Associada a mTOR , Serina-Treonina Quinases TOR/metabolismo , Fator de Transcrição 4 , Fatores de Transcrição/genética , Regulação para Cima/efeitos dos fármacos , beta Catenina/genéticaRESUMO
OBJECTIVE: This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats. METHOD: Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively. RESULTS: Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity. CONCLUSIONS: Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status.
Assuntos
Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Mel , Leptospermum/química , Estresse Oxidativo/efeitos dos fármacos , Fatores Etários , Animais , Catalase/análise , Ensaio Cometa , Glutationa Peroxidase/análise , Masculino , Malondialdeído/sangue , Ratos , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Superóxido Dismutase/análise , Fatores de TempoRESUMO
OBJECTIVE: This study aimed to determine the effect of manuka honey on the oxidative status of middle-aged rats. METHOD: Twenty-four male Sprague-Dawley rats were divided into young (2 months) and middle-aged (9 months) groups. They were further divided into two groups each, which were either fed with plain water (control) or supplemented with 2.5 g/kg body weight of manuka honey for 30 days. The DNA damage level was determined via the comet assay, the plasma malondialdehyde level was determined using high performance liquid chromatography, and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione peroxidase and catalase) were determined spectrophotometrically in the erythrocytes and liver. The antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl and ferric reducing/antioxidant power assays, and the total phenolic content of the manuka was analyzed using UV spectrophotometry and the Folin-Ciocalteu method, respectively. RESULTS: Supplementation with manuka honey reduced the level of DNA damage, the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. However, the glutathione peroxidase activity was increased in the erythrocytes of middle-aged rats given manuka honey supplementation. The catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation. Manuka honey was found to have antioxidant activity and to have a high total phenolic content. These findings showed a strong correlation between the total phenolic content and antioxidant activity. CONCLUSIONS: Manuka honey reduces oxidative damage in young and middle-aged rats; this effect could be mediated through the modulation of its antioxidant enzyme activities and its high total phenolic content. Manuka honey can be used as an alternative supplement at an early age to improve the oxidative status. .