RESUMEN
The cyclinD1 is an emerging potent therapeutic drug target in the treatment of ovarian cancer. CyclinD1, Cdks phosphorylation regulates cell cycle and controls transcription. For this reason, CyclinD1 have been subject to extensive cell cycle- related research, and consequently various therapeutic inhibitor drugs have been developed to these protein targets. In the present study we identified that the expression levels of Bcl-2, Bax, caspase 8, 9 and cyclinD1 using Q-PCR method in SKOV3 cell lines treated with Isochamanetin. The viability and migratory inhibition ability also studied to know the mode of cell death. Further the expression levels of Bcl-2, caspase8,9, Cytochrome C and CyclinD1 were significantly down regulated in SKOV3 cancer cells treated with isochamanetin, a specific binding molecule to CyclinD1. The therapeutic molecules found by a high through put insilicoscreen of this pocket exhibit cytostatic nature and reduce protein levels of cell cycle. The novel structural site on CyclinD1, which is well conserved and inhibits the SKOV3 cells from G0-G1 to S phase cell cycle progression. The current result suggests that isochamanetin serves as potent binding agent to the cyclinD1.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Chalconas/farmacología , Ciclina D1/antagonistas & inhibidores , Flavanonas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Antineoplásicos Fitogénicos/química , Asteraceae/química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciclina D1/metabolismo , Femenino , Flavanonas/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Espectroscopía de Resonancia Magnética , Simulación del Acoplamiento Molecular , Estructura Molecular , Neoplasias Ováricas/metabolismo , Mapas de Interacción de ProteínasRESUMEN
The hypoglycemic effect of the aqueous extract of the seeds of Mucuna pruriens was investigated in normal, glucose load conditions and streptozotocin (STZ)-induced diabetic rats. In normal rats, the aqueous extract of the seeds of Mucuna pririens (100 and 200 mg/kg body weight) significantly (P<0.001) reduced the blood glucose levels after an oral glucose load from 127.5+/-3.2 to 75.6+/-4.8 mg% 2 h after oral administration of seed extract. It also significantly lowered the blood glucose in STZ diabetic rats from 240.5+/-7.2 to 90.6+/-5.6 mg% after 21 days of daily oral administration of the extract (P<0.001). Thus, this study shows that M. pruriens has an anti-hyperglycemic action and it could be a source of hypoglycemic compounds.