title: Niclosamide inhibits colon cancer progression through downregulation of the Notch pathway and upregulation of the tumor suppressor miR-200 family.
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.
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Suliman
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Heya
authors.initials: H
authors.lastname: Na
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Ailton L L
authors.initials: AL
authors.lastname: Ribeiro
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Bachir
authors.initials: B
authors.lastname: Niang
authors.affiliation: Department of Clinical Laboratory Science, Asmara College of Health Sciences, Asmara, Eritrea.
authors.forename: Abdu Salim
authors.initials: AS
authors.lastname: Hamid
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Clinical Biochemistry, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zuo
mesh_terms: D000969:Antinematodal Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009534:Niclosamide / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000378:metabolism; D051883:Receptor, Notch2 / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000969:Antinematodal Agents; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D051880:Receptors, Notch; D009534:Niclosamide