Niclosamide, an oral antihelmintic drug, exhibits antimetastatic activity in hepatocellular carcinoma cells through downregulating twist-mediated CD10 expression

Ming Hsien Chien, Yung Chuan Ho, Shun Fa Yang, Yi Chieh Yang, Szu Yu Lai, Wan Shen Chen, Ming Jenn Chen, Chao Bin Yeh

Research output: Contribution to journalArticle

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, especially, in eastern Asia, and its prognosis is poor once metastasis occurs. Niclosamide, a US Food and Drug Administration-approved antihelmintic drug, was shown to inhibit the growth of various cancers including HCC, but the effect of niclosamide on cell motility and the underlying mechanism have not yet been completely defined. The present study demonstrated that niclosamide, at 0-40 nM, concentration-dependently inhibited wound closure and the migratory/invasive capacities of human Huh7 and SK-Hep-1 HCC cells without exhibiting cytotoxicity. A protease array analysis showed that CD10 was dramatically downregulated in Huh7 cells after niclosamide treatment. Western blot and flow cytometric assays further demonstrated that CD10 expression was concentration-dependently downregulated in Huh7 and SK-Hep-1 cells after niclosamide treatment. Mechanistic investigations found that niclosamide suppressed Twist-mediated CD10 transactivation. Moreover, knockdown of CD10 expression by CD10 small interfering RNA in HCC cells suppressed cell migratory/invasive abilities and overexpression of CD10 relieved the migration inhibition induced by niclosamide. Taken together, our results indicated that niclosamide could be a potential agent for inhibiting metastasis of HCC, and CD10 is an important target of niclosamide for suppressing the motility of HCC cells.

Original languageEnglish
JournalEnvironmental Toxicology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Niclosamide
Anthelmintics
motility
Hepatocellular Carcinoma
drug
Down-Regulation
Cells
Pharmaceutical Preparations
RNA
cancer
assay
Neoplasm Metastasis
Far East
United States Food and Drug Administration
Cytotoxicity
Small Interfering RNA
Transcriptional Activation
Cell Movement
Assays
Neoplasms

Keywords

  • CD10
  • Hepatocellular carcinoma
  • Invasion
  • Migration
  • Niclosamide

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

Cite this

Niclosamide, an oral antihelmintic drug, exhibits antimetastatic activity in hepatocellular carcinoma cells through downregulating twist-mediated CD10 expression. / Chien, Ming Hsien; Ho, Yung Chuan; Yang, Shun Fa; Yang, Yi Chieh; Lai, Szu Yu; Chen, Wan Shen; Chen, Ming Jenn; Yeh, Chao Bin.

In: Environmental Toxicology, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Chien, Ming Hsien

AU - Ho, Yung Chuan

AU - Yang, Shun Fa

AU - Yang, Yi Chieh

AU - Lai, Szu Yu

AU - Chen, Wan Shen

AU - Chen, Ming Jenn

AU - Yeh, Chao Bin

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