Abstract
In the present study, a flavonoid was isolated from Origanum vulgare and identified as didymin. The effect and mechanism of O. vulgare didymin (OVD) on human HepG2 liver carcinoma cell was then assessed. Our results showed that OVD strongly inhibited the viability, clonogenicity and migration of HepG2 cells. OVD significantly induced apoptosis and induced cell cycle arrest at G2/M phase by regulating cyclin B1, cyclin D1 and CDK4. The anti-proliferative and pro-apoptotic effects were associated with changes in the Bcl-2/Bax ratio and induction of caspase-mediated apoptosis. Moreover, OVD attenuated the mitochondrial membrane potential, accompanied by the release of cytochrome c. In addition, OVD inhibited the ERK/MAPK and PI3K/Akt pathways by increasing the level of Raf kinase inhibitor protein (RKIP). Our study indicates that OVD induces apoptosis against of HepG2 cells through mitochondrial dysfunction and inactivation of the ERK/MAPK and PI3K/Akt pathways by up-regulating RKIP.
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