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

  • Authors:
    • Fang-Liang Huang
    • Sheng-Jie Yu
    • En-Chih Liao
    • Long-Yuan Li
    • Pei-Wen Shen
    • Chia-Ling Li
  • View Affiliations / Copyright

    Affiliations: Children's Medical Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C., Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan, R.O.C., Institute of Biomedical Sciences, MacKay Medical College, New Taipei City 25245, Taiwan, R.O.C., Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan, R.O.C., Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan, R.O.C.
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 30
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    Published online on: December 15, 2021
       https://doi.org/10.3892/or.2021.8241
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Huang F, Yu S, Liao E, Li L, Shen P and Li C: Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy. Oncol Rep 47: 30, 2022.
APA
Huang, F., Yu, S., Liao, E., Li, L., Shen, P., & Li, C. (2022). Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy. Oncology Reports, 47, 30. https://doi.org/10.3892/or.2021.8241
MLA
Huang, F., Yu, S., Liao, E., Li, L., Shen, P., Li, C."Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy". Oncology Reports 47.2 (2022): 30.
Chicago
Huang, F., Yu, S., Liao, E., Li, L., Shen, P., Li, C."Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy". Oncology Reports 47, no. 2 (2022): 30. https://doi.org/10.3892/or.2021.8241
Copy and paste a formatted citation
x
Spandidos Publications style
Huang F, Yu S, Liao E, Li L, Shen P and Li C: Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy. Oncol Rep 47: 30, 2022.
APA
Huang, F., Yu, S., Liao, E., Li, L., Shen, P., & Li, C. (2022). Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy. Oncology Reports, 47, 30. https://doi.org/10.3892/or.2021.8241
MLA
Huang, F., Yu, S., Liao, E., Li, L., Shen, P., Li, C."Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy". Oncology Reports 47.2 (2022): 30.
Chicago
Huang, F., Yu, S., Liao, E., Li, L., Shen, P., Li, C."Niclosamide suppresses T‑cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy". Oncology Reports 47, no. 2 (2022): 30. https://doi.org/10.3892/or.2021.8241
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