Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a common pediatric malignancy, characterized by the abnormal presence of immature T-cell progenitors. Conventional treatments for T-ALL fail to prevent or cure the disease, with a high-risk of recurrence after the first remission. Thus, medical options are in demand to develop novel therapies for patients suffering with T-ALL. Niclosamide, a traditional oral anti-helminthic drug, has been reported to be a potential anticancer agent that regulates intracellular signaling pathways. Few studies have yet investigated the effects of niclosamide on the development of T-ALL. Here, the present study aimed to investigate the anti-leukemia effects of niclosamide on T-ALL. We first hypothesized that the suppressive effects of niclosamide on the tumor growth of T-ALL are exerted by regulating autophagy and apoptosis. Following niclosamide treatment, T-ALL cell viability was evaluated using MTT assay, and apoptosis with Annexin V/propidium iodide staining. In T-ALL cells treated with niclosamide, changes in apoptosis- and autophagy-related proteins were analyzed by western blotting. In addition, in an in vivo model, T-ALL xenograft mice were used to study the anti-leukemia effects of niclosamide. The results showed that niclosamide significantly reduced the viability of Jurkat and CCRF-CEM T-ALL cells in both a dose- and time-dependent manner. Niclosamide significantly activated the early and late phases of apoptosis in Jurkat (at 2 µM) and CCRF-CEM cells (at 1 µM). Furthermore, niclosamide upregulated protein expression of cleaved caspase-3 and LC3B, while downregulated those of Bcl-2 and p62, in a dose-dependent manner in both Jurkat and CCRF-CEM cells. The in vivo results showed that niclosamide treatment significantly suppressed tumor growth and the disease progression in T-ALL xenograft mice by activating cleaved caspase-3 and LC3B. We conclude that niclosamide plays an anti-leukemia role, and that it represents a novel approach for the treatment of T-ALL.