Contributions
Abstract: PB1617
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is a common hematological malignancy in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL.
Aims
In this study, the anti-leukemic effect and the potential molecular mechanisms of butein on ALL were investigated.
Methods
We examined the rate of apoptosis of CEM-C7 (T-ALL), CEM-C1 (T-ALL), MOLT-4 (T-ALL), RS4-11 (B-ALL) cell lines and primary ALL blasts exposed to various concentrations of butein for 24 h using the flow cytometry. We tested the expression of the caspase-9, poly ADP-ribose polymerase (PARP), nuclear Forkhead Class box O3a (FOXO3a) and BCL-2 interacting mediator of cell death (BIM) using western blot assay. We established the xenograft mouse model to examine the anti-leukemic effect of butein in vivo.
Results
Butein was found to significantly induce the cellular apoptosis of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also activated the cleavage of caspase-9 and PARP. We also found that butein promoted FOXO3a localization, enhanced the binding of FOXO3a on the BIM gene promoter and then increased the expression of BIM. Moreover, we showed that FOXO3a knockdown significantly decreased the apoptosis by butein, whereas overexpression of FOXO3a enhanced the butein-induced apoptosis. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the apoptosis by butein through decreasing the expression of BIM. Furthermore, treatment with butein was highly efficacious in vivo, with enhanced reduction of tumor burden in a xenograft model of ALL.
Conclusion
Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a and caspase-dependent apoptotic pathways.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): FoxO3a, Caspase, Apoptosis, Acute lymphoblastic leukemia
Abstract: PB1617
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) is a common hematological malignancy in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL.
Aims
In this study, the anti-leukemic effect and the potential molecular mechanisms of butein on ALL were investigated.
Methods
We examined the rate of apoptosis of CEM-C7 (T-ALL), CEM-C1 (T-ALL), MOLT-4 (T-ALL), RS4-11 (B-ALL) cell lines and primary ALL blasts exposed to various concentrations of butein for 24 h using the flow cytometry. We tested the expression of the caspase-9, poly ADP-ribose polymerase (PARP), nuclear Forkhead Class box O3a (FOXO3a) and BCL-2 interacting mediator of cell death (BIM) using western blot assay. We established the xenograft mouse model to examine the anti-leukemic effect of butein in vivo.
Results
Butein was found to significantly induce the cellular apoptosis of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also activated the cleavage of caspase-9 and PARP. We also found that butein promoted FOXO3a localization, enhanced the binding of FOXO3a on the BIM gene promoter and then increased the expression of BIM. Moreover, we showed that FOXO3a knockdown significantly decreased the apoptosis by butein, whereas overexpression of FOXO3a enhanced the butein-induced apoptosis. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the apoptosis by butein through decreasing the expression of BIM. Furthermore, treatment with butein was highly efficacious in vivo, with enhanced reduction of tumor burden in a xenograft model of ALL.
Conclusion
Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a and caspase-dependent apoptotic pathways.
Session topic: 1. Acute lymphoblastic leukemia - Biology
Keyword(s): FoxO3a, Caspase, Apoptosis, Acute lymphoblastic leukemia