Abstract
Acute lymphoblastic leukemia (ALL) is a significant cancer of children resulting from the clonal proliferation of lymphoid precursors with arrested maturation. Although chemotherapeutic approaches have been achieving successful remission for the majority of cases of childhood ALL, development of resistance to chemotherapy has been observed. Thus, new therapeutic approaches are required to improve patient's prognosis. Therefore, we investigated the anticancer potential of curcumin in ALL. We tested a panel of B-precursor ALL (B-Pre-ALL) cell lines with various translocations after treatment with different doses of curcumin. Curcumin suppresses the viability in a concentration-dependent manner in 697, REH, SupB15, and RS4;11 cells (doses from 0 to 80 μM). Curcumin induces apoptosis in B-Pre-ALL cell lines via activation of caspase-8 and truncation of BID. Curcumin treatment increased the ratio of Bax/Bcl-2 and resulted in a leaky mitochondrial membrane that led to the discharge of cytochrome c from the mitochondria to the cytoplasm, the activation of caspase 3 and the cleavage of PARP. Curcumin treatment of B-Pre-ALL cell lines induced a dephosphorylation of the constitutive phosphorylated AKT/PKB and a down-regulation of the expression of cIAP1, and XIAP. Moreover, curcumin mediates its anticancer activity by the generation of reactive oxygen species. Finally, the suboptimal doses of curcumin potentiated the anticancer activity of cisplatin. Altogether, these results suggest an important therapeutic role of curcumin, acting as a growth suppressor of B-Pre-ALL by apoptosis via inactivation of AKT/PKB and down-regulation of IAPs and activation of intrinsic apoptotic pathway via generation of Reactive Oxygen Species (ROS). Our interesting findings raise the possibility of considering curcumin as a potential therapeutic agent for the treatment of B-Pre-ALL.
Highlights
Acute lymphoblastic leukemia (ALL) is a blood related human malignancy
Survival rate for leukemia patients has been shown to reach 90% in children aged up to 14 years old while it drops to 40% in adults between 25 and and it is almost 15% for those aged or older [3]
The prognosis for ALL is strongly influenced by the age at diagnosis, with lower survival described in adult population
Summary
Acute lymphoblastic leukemia (ALL) is a blood related human malignancy. It is commonly found in the pediatric population and is designated as B-precursor acute lymphoblastic leukemia (B-Pre-ALL). B-Pre-ALL is an aggressive hematological malignancy that frequently occurs in children [1, 2]. Survival rates improved continuously in 0– 14 year old patients who tend to do much better than older people. Survival rate for leukemia patients has been shown to reach 90% in children aged up to 14 years old while it drops to 40% in adults between 25 and and it is almost 15% for those aged or older [3]. Personalized and targeted therapies are urgently needed to enhance the prognosis of ALL patients
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