The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma cell therapy.

摘要: N-Butylidenephthalide (BP), isolated from the chloroform extract of Angelica sinensis, has been examined for its antitumor effects on glioblastoma multiforme brain tumors; however, little is known about hepatocellular carcinoma cells. Two cell lines, HepG2 and J5, were treated with either N-butylidenephthalide or a vehicle, viability apoptosis evaluated. Apoptosis-related mRNA proteins expressed, including orphan receptor family Nurr1, NOR-1, Nur77, evaluated as well effect in an vivo xenograft model. caused growth inhibition both lines at 25 μg/ml. Furthermore, N-butylidenephthalide-induced seems to be related Nur77 translocation nucleus cytosol, which leads cytochrome c release caspase-3-dependent apoptosis. N-Butylidenephthalide-related tumor was associated phosphatidylinositol 3-kinase/protein kinase B (AKT)/glycogen synthase kinase-3β rather than mitogen-activated protein C pathway. Blockade AKT activation enhanced proliferation induction phosphor-Bcl-2 proteins. Besides, increasing by BP via transfection wild-type cAMP-response element-binding (CREB) into suppressed dominant phosphorylation site mutation CREB. This finding suggested CREB pathway also partly involved BP. Administration showed similar antitumoral J5 tumors. induced cells, vitro vivo, suggesting potential clinical use this compound improving prognosis