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J Transl Med. 2011 Apr 21;9:45. doi: 10.1186/1479-5876-9-45.

Pro-apoptotic activity of α-bisabolol in preclinical models of primary human acute leukemia cells.

Author information

1
Department of Medicine, Section of Hematology, University of Verona, Italy. fabrizio.vinante@univr.it

Abstract

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.

PMID:
21510902
PMCID:
PMC3112094
DOI:
10.1186/1479-5876-9-45
[Indexed for MEDLINE]
Free PMC Article

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