RESUMEN
We studied the effect of 4-acetyl-12,13-epoxyl-9-trichothecene-3, 15-diol (AETD) isolated from Isaria japonica, one of the most popular Chinese fungal medicines, on the induction of apoptosis in rat bladder carcinoma NBT-II cells. AETD was cytotoxic to NBT-II cells, and this cytotoxic effect appears to be attributed to its induction of apoptotic cell death, as AETD induced nuclear morphological changes and internucleosomal DNA fragmentation, and increased the proportion of hypodiploid cells and activity of caspase-3. AETD treatment also decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the pro-apoptotic protein Bax. These results provide important information in understanding the mechanism(s) of AETD-induced apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tricotecenos/farmacología , Neoplasias de la Vejiga Urinaria/patología , Animales , Carcinoma/metabolismo , Caspasa 3 , Caspasas/metabolismo , Línea Celular Tumoral/efectos de los fármacos , Fragmentación del ADN , ADN de Neoplasias/análisis , Microscopía Fluorescente , Ratas , Neoplasias de la Vejiga Urinaria/metabolismo , Proteína X Asociada a bcl-2RESUMEN
(3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethylperhydro-1,4-oxazine-2,5-dione (1) was isolated from the fruiting bodies of Isaria japonica as an apoptosis-inducing agent. The complete structural assignment of the compound was accomplished on the basis of spectroscopic methods and chemical transformations. Compound 1 induced apoptotic cell death of the human leukemia cells (HL-60) in a dose-dependent manner, ranging from 5.0 microg/ml to 100.0 microg/ml.