bisabolol and Leukemia

Medicinal plants represent an important resource in new drug research. Antioxidant properties of plants can help to scavenge reactive oxygen species. The objective of this work was to evaluate the genotoxic, antigenotoxic, tumoricidal, and apoptotic effect of some major phenols (apigenin, bisabolol, and protocatechuic acid) from two medicinal plants, Matricaria chamomilla and Uncaria tomentosa. The wing spot test of Drosophila melanogaster was used to evaluate the genotoxicity and antigenotoxicity of the three phenols. The human model of HL-60 leukemia cells was used for the assessment of the cytotoxic effect, growth, and cellular viability. The apoptotic effect was evaluated using a DNA fragmentation assay based on the formation of internucleosomal units. Protocatechuic acid (0.25 and 1 mM), apigenin (0.46 and 1.85 mM), and bisabolol (0.56 and 2.24 mM) did not exhibit any genotoxic effect. The three phenols showed an antigenotoxic effect against the hydrogen peroxide effect and also exhibited tumoricidal activity. Apigenin (2.24-35.96 mM) showed a lower 50% inhibitory concentration (0.75 and 3.87 mM for the trypan blue test and WST-8 colorimetric assay, respectively) than bisabolol and protocatechuic acid. These phenolics also induced apoptosis in HL-60 leukemia cells. This study suggests that the antioxidant activity of Chamomilla and Uncaria could be partially responsible of their beneficial activity.

Topics: Animals; Antimutagenic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Apigenin; Apoptosis; DNA Fragmentation; Drosophila; HL-60 Cells; Humans; Hydrogen Peroxide; Hydroxybenzoates; Leukemia; Matricaria; Monocyclic Sesquiterpenes; Phenols; Phytotherapy; Plant Extracts; Sesquiterpenes; Uncaria

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