bisabolol and Blast-Crisis

We previously demonstrated that the plant-derived agent α-bisabolol enters cells via lipid rafts, binds to the pro-apoptotic Bcl-2 family protein BID, and may induce apoptosis. Here we studied the activity of α-bisabolol in acute leukemia cells.. We tested ex vivo blasts from 42 acute leukemias (14 Philadelphia-negative and 14 Philadelphia-positive B acute lymphoid leukemias, Ph-/Ph+B-ALL; 14 acute myeloid leukemias, AML) for their sensitivity to α-bisabolol in 24-hour dose-response assays. Concentrations and time were chosen based on CD34+, CD33+my and normal peripheral blood cell sensitivity to increasing α-bisabolol concentrations for up to 120 hours.. A clustering analysis of the sensitivity over 24 hours identified three clusters. Cluster 1 (14 ± 5 μM α-bisabolol IC50) included mainly Ph-B-ALL cells. AML cells were split into cluster 2 and 3 (45 ± 7 and 65 ± 5 μM IC50). Ph+B-ALL cells were scattered, but mainly grouped into cluster 2. All leukemias, including 3 imatinib-resistant cases, were eventually responsive, but a subset of B-ALL cells was fairly sensitive to low α-bisabolol concentrations. α-bisabolol acted as a pro-apoptotic agent via a direct damage to mitochondrial integrity, which was responsible for the decrease in NADH-supported state 3 respiration and the disruption of the mitochondrial membrane potential.. Our study provides the first evidence that α-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells.

Topics: Adolescent; Adult; Apoptosis; Benzamides; BH3 Interacting Domain Death Agonist Protein; Blast Crisis; Blood Cells; Cell Respiration; Cluster Analysis; Culture Media; Drug Screening Assays, Antitumor; Female; Fusion Proteins, bcr-abl; Humans; Imatinib Mesylate; Leukemia; Male; Membrane Potential, Mitochondrial; Middle Aged; Mitochondria; Models, Biological; Monocyclic Sesquiterpenes; Mutation; Piperazines; Pyrimidines; Sesquiterpenes; Solubility; Time Factors; Tumor Cells, Cultured; Young Adult