Niclosamide inhibits colon cancer progression through downregulation of the Notch pathway and upregulation of the tumor suppressor miR-200 family

Suliman,Mohammed   A.; Zhang,Zhenxing; Na,Heya; Ribeiro,Ailton   L.L.; Zhang,Yu; Niang,Bachir; Hamid,Abdu  Salim; Zhang,Hua; Xu,Lijie; Zuo,Yunfei

doi:10.3892/ijmm.2016.2689

Niclosamide inhibits colon cancer progression through downregulation of the Notch pathway and upregulation of the tumor suppressor miR-200 family

Authors:
- Mohammed A. Suliman
- Zhenxing Zhang
- Heya Na
- Ailton L.L. Ribeiro
- Yu Zhang
- Bachir Niang
- Abdu Salim Hamid
- Hua Zhang
- Lijie Xu
- Yunfei Zuo
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Affiliations: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Clinical Laboratory Science, Asmara College of Health Sciences, Asmara, Eritrea
Published online on: July 22, 2016 https://doi.org/10.3892/ijmm.2016.2689
Pages: 776-784
Copyright: © Suliman et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is among the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for the development of new therapeutic approaches for the treatment of CRC. Accumulating evidence has revealed that niclosamide, an anthelminthic drug, exerts antitumor activity in several types of cancer, including colon cancer. However, the underlying molecular mechanisms responsible for the effects of this drug remain elusive. Previous studies have shown that the aberrant Notch signaling pathway contributes to the carcinogenesis of colon cancer. Herein, we examined the effects of niclosamide on the growth, migration and apoptosis of colon cancer cells, and the role of the Notch signaling pathway. By performing MTT, wound-healing and Transwell migration assays, we observed that niclosamide suppressed the growth and migration of colon cancer cells, and flow cytometry demonstrated that cell apoptosis was induced. This was associated with the decreased protein expression of Notch1, Notch2, Notch3 and Hey1, and the increased expression of the tumor suppressor microRNA (miR or miRNA)‑200 family members (miR‑200a, miR-200b, miR-200c, miR-141 and miR-429) that are typically downregulated in colon cancer. Collectively, these findings demonstrate that niclosamide potentially inhibits the progression of colon cancer by downregulating Notch signaling and by upregulating the miR-200 family members.

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