| Autor: |
Cavalieri E, Rigo A, Bonifacio M, Carcereri de Prati A, Guardalben E, Pizzolo G, Suzuki H, Vinante F., BERGAMINI, CHRISTIAN, FATO, ROMANA |
| Přispěvatelé: |
Cavalieri E, Rigo A, Bonifacio M, Carcereri de Prati A, Guardalben E, Bergamini C, Fato R, Pizzolo G, Suzuki H, Vinante F. |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
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| Popis: |
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our study provides the first evidence that α-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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