title: Carnosic acid induces apoptosis associated with mitochondrial dysfunction and Akt inactivation in HepG2 cells.
abstract: Carnosic acid (CA), a phenolic diterpene isolated from rosemary, shows potential benefits in health promotion and disease prevention. In the present study, the cytotoxic and apoptotic-inducing effects of CA on human hepatocellular carcinoma HepG2 cells were investigated. The MTT assay results indicated that CA decreased cell viability in HepG2 cells in a dose-dependent manner. Treatment with CA caused a rapid Caspase-3 activation and subsequently proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), both of which were markers of cells undergoing apoptosis. CA also dissipated mitochondrial membrane potential and decreased the ratio of Bcl-2/Bax protein, which mediated cytosolic translocation of cytochrome c from the mitochondria. Furthermore, CA reduced the phosphorylation of Akt, which was partially inhibited by insulin, an activator of phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. In conclusion, our data suggest that the mitochondrial dysfunction and deactivation of Akt may contribute to the apoptosis-inducing effects of CA.
authors.affiliation: College of Food and Biological Engineering, Zhengzhou University of Light Industry , Zhengzhou , China.
authors.forename: Qisen
authors.initials: Q
authors.lastname: Xiang
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Ma
authors.forename: Jilin
authors.initials: J
authors.lastname: Dong
authors.forename: Ruiling
authors.initials: R
authors.lastname: Shen
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D027542:Rosmarinus / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D045784:Abietanes; D053148:Caspase 3; D045304:Cytochromes c; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C018381:salvin
keywords: Akt; Caspase-3; apoptosis; carnosic acid; mitochondria