Augmentation by carnosic acid of apoptosis in human leukaemia cells induced by arsenic trioxide via upregulation of the tumour suppressor PTEN

Carnosic acid is a strong dietary antioxidant derived from rosemary. Here, we have demonstrated that carnosic acid decreased viability of the human promyelocytic leukaemia cell line, HL-60, in dose- and time-dependent manners, and induced G(1) arrest and apoptosis. Carnosic acid also augmented these effects when induced by a low (physiological) concentration of arsenic trioxide, which was associated with upregulation of p27 and activation of caspase-9. These effects appeared to be mediated by the induction of phosphatase and tensin homologue (PTEN) expression. These findings indicate that PTEN plays an important role in the coordinated induction of apoptosis and G(1) arrest by carnosic acid and arsenic trioxide. Carnosic acid may have potential as an adjuvant in arsenic trioxide-induced apoptosis therapy due to its anticipated safety and great potency in enhancing the apoptosis-inducing action of a low concentration of arsenic trioxide.