RESUMO
The proapoptotic effect of anphen (the effect on the level of the antiapoptotic protein Bcl-2) was investigated by immunoblotting. Incubation of Lewis carcinoma cell suspension with anphen at a concentration of 10-6 M for 0-3 h caused a 80% reduction in the level of the Bcl-2 protein and its homodimer. In vivo, when administered for 4 days to outbred mice, anphen (10-4 M) induced a decrease in the level of the Bcl-2 homodimer in the spleen cells by 20% and an increase in the content of the Bad protein (apoptosis activator) and the Bcl-XL protein. The antitumor effect of anphen may be due to blocking the hydrophobic pocket of the Bcl-2 protein.
Assuntos
Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Malonatos/uso terapêutico , Fenóis/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Padrões de ReferênciaRESUMO
We studied the development of Lewis carcinoma and possible antitumor effect of preliminary administered antioxidant anphen. The tumor was intramuscularly transplanted to C57Bl×DBA mice (7×106 cells per mouse). According to immunoblotting results, the content of anti-apoptotic Bcl-2 protein steadily decreased starting from post-transplantation day 11. In few days, its content decreased by 15-20% and soon the animals died. After administration of anphen, the content of Bcl-2 decreased more rapidly than in the control. Atomic force microscopy revealed a decrease in the mean volume of erythrocytes and then increase in this parameter at the terminal stage of tumor growth. These findings suggest that anphen does not affect the tumor growth rate and mouse lifespan, but enhances apoptosis of blood cells of animals with Lewis carcinoma at the terminal stages of tumor growth.
