Induction of Apoptosis by Rosemary Polyphenols in HL-60 Cells

Abstract

Rosemary (Rosmarinus officinalis Labiatae) and its extract are widely used in food processing and herbal medicine. Carnosic acid, carnosol, rosmarinic acid and ursolic acid are biologically active chemicals isolated from rosemary. Carnosol and ursolic acid have been shown to inhibit tumor initiation and promotion. In the present study, carnosic acid, carnosol, and ursolic acid were found to induce apoptotic (sub Gl) peak and typical DNA fragmentation in a concentration- and timedependent manner. Carnosic acid, carnosol and ursolic acid all activated caspase-3, -9 and induced the cleavage of down stream substrates such as poly-(ADP-ribose) polymerase (PARP) and the degradation of DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Carnosic acid, carnosol and ursolic acid also induced mitochondrial membrane depolarization, intracellular reactive oxygen species (ROS) generation and the release of cytochrome c from mitochondria into cytosol. Taken together, these data suggest that carnosic acid, carnosol and ursolic acid induce apoptosis in HL-60 cells through the release of cytochrome c to the cytosol and activation of the caspases cascade. The induction of apoptosis by carnosic acid, carnosol and ursolic acid may be attributed to their cancer chemopreventive actions.