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Carnosic acid activates AMPK, inhibits Akt and inhibits H1299 human lung cancer cell survival

Non‐small cell lung cancer (NSCLC) represents 80% of all lung cancers and is characterized by low survival rates due to chemotherapy and radiation resistance. Thus, finding alternative treatments to reduce NSCLC proliferation and survival is of high importance. The survival pathways of Akt, the energy sensor AMP‐activated protein kinase (AMPK), and the apoptotic protein poly (ADP‐ribose) polymerase (PARP) are key modulators of cancer cell growth and survival. In previous studies, we found inhibition of NSCLC proliferation and survival by rosemary extract but the exact components responsible for the anticancer effects and the cellular mechanisms involved are not known. Rosemary extract contains many polyphenols including carnosic acid (CA). The objectives of the present study were to examine the effects of CA on NSCLC cell survival and apoptosis, and to investigate its effects on Akt, AMPK and PARP. The human NSCLC cell line H1299 was used. Clonogenic cell survival assays were performed to examine the effects of CA on cell survival, and immunoblotting with phospho‐specific antibodies was performed to examine signaling events. CA dose‐dependently inhibited H1299 cell survival. A significant inhibition of Akt phosphorylation/activation and enhanced AMPK phosphorylation/activation was seen with 25 and 50 mM CA while the total levels of each protein were not affected. PARP cleavage, an indicator of apoptosis, was enhanced by carnosic acid treatment. Our findings indicate that CA may have robust anticancer properties in NSCLC, and strongly support the need for further studies to investigate its role against lung cancer.