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.

• Akt
• apoptosis
• carnosic acid
• Caspase-3
• mitochondria

Declaration of interest

The authors report that they have no conflicts of interest. The authors alone are responsible for the content and writing of the paper. Financial supports from the Scientific Research Foundation for Doctoral Scholars of Zhengzhou University of Light Industry (Grant no. 2013BSJJ079) are gratefully acknowledged.