Abstract
BackgroundWe 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.MethodsWe 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.ResultsA 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.ConclusionOur study provides the first evidence that α-bisabolol is a pro-apoptotic agent for primary human acute leukemia cells.
Highlights
We previously demonstrated that the plant-derived agent a-bisabolol enters cells via lipid rafts, binds to the pro-apoptotic Bcl-2 family protein BID, and may induce apoptosis
We have previously found that it enters cells via lipid-rafts, interacts directly with BID, a pro-apoptotic BH3-only Bcl-2 family protein, and induces apoptosis [3]
The present study shows that a-bisabolol enters acute leukemic cells, where it disrupts the mitochondrial membrane potential and triggers apoptosis
Summary
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 a-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 a-bisabolol concentrations for up to 120 hours. Patients and ethical requirements Blasts from 28 patients with B-lineage ALL (14 Ph-, 14 Ph+B-ALL) and 14 with AML diagnosed at our institution, as well as blood and bone marrow cells from five healthy control donors, were collected after written informed consent was obtained, according to Italian law. The diagnosis of B-ALL or AML and their subtypes was based on clinical findings and on established morphological, cytochemical, cytofluorimetric, cytogenetic and molecular features of peripheral blood and bone marrow cells. AML patients received three induction courses according to standard AML treatment (1st course: 3-day idarubicin + 7-day AraC by continuous i.v. infusion; 2nd course: 3-day idarubicin + 3-day high-dose AraC; 3rd course: 3-day high-dose AraC). Allogeneic bone marrow transplantation was performed during the first complete remission in four Ph-B-ALL cases and four Ph+B-ALL cases
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
