title: Didymin induces apoptosis through mitochondrial dysfunction and up-regulation of RKIP in human hepatoma cells.
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.
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Wei
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Facheng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Nie
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shengjuan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Chunyuang
authors.initials: C
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China; Department of Biochemistry, University of Arkansas Medical School, 4301 W. Markham, Little Rock, AR 72205-7199, USA.
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China. Electronic address: gxLx60@163.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D045304:Cytochromes c / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018797:Cell Cycle Proteins; D005419:Flavonoids; D006027:Glycosides; D049488:Phosphatidylethanolamine Binding Protein; C552234:didymin; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9
keywords: Didymin; ERK/MAPK pathway; Mitochondrial dysfunction; PI3K/Akt pathway; RKIP