Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia cells

Carnosol, a phenolic compound extracted from the herb rosemary has been reported to have anti-cancer activity. We investigated whether carnosol was cytotoxic against several pro-B and pre-B acute lymphoblastic leukemia (ALL) lines. In all ALL lines tested, carnosol induced apoptotic cell death distinguished by loss of nuclear DNA, externalization of cell membrane phosphatidylserine, and depolarization of mitochondrial membranes. Flow cytometric measurement of Bcl-2 protein levels revealed that carnosol induced a 34–53% decrease in Bcl-2 in the cell population exhibiting a viable phenotype prior to detectable apoptotic changes in morphology. These results suggest that carnosol may be useful as a novel chemotherapeutic agent against B-lineage leukemias, and possibly other types of cancers that express high levels of the protective protein, Bcl-2.