Carnosol, from the herb rosemary, has been shown to induce apoptotic cell death in high-risk pre-B
acute lymphoblastic leukemia (ALL). In the present study,
carnosol was tested for its ability to sensitize
leukemia cells to chemotherapeutic agents.
Carnosol reduced the percentage of cell death in the
pre-B ALL lines SEM, RS4;11, and REH when combined with
cytarabine,
methotrexate, or
vincristine compared to the chemotherapeutic agents alone. Analysis of
DNA strand breaks by
terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that
carnosol delayed DNA cleavage in the cells when combined with chemotherapeutic drugs. Co-treatment of the cells with
carnosol and chemotherapeutic drugs did not reduce mitochondrial membrane depolarization compared to the
drug treatment alone. Time course analysis of
caspase-3 activation by flow cytometry showed co-treatment with
carnosol and drugs increased the activation of
caspase-3 above that observed for the chemotherapeutic drugs alone. A lower percentage of
caspase-3 positive cells progressed to an apoptotic phenotype when co-treated with
carnosol and the chemotherapeutic drugs compared to drugs alone. These data show that
carnosol blocks the terminal apoptotic events induced by chemotherapeutic drugs and suggest that increased dietary intake of
carnosol may potentially decrease the effectiveness of some standard
chemotherapy treatments used for
leukemia.