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Niclosamide, an oral antihelmintic drug, exhibits antimetastatic activity in hepatocellular carcinoma cells through downregulating twist‐mediated CD10 expression
Author(s) -
Chien MingHsien,
Ho YungChuan,
Yang ShunFa,
Yang YiChieh,
Lai SzuYu,
Chen WanShen,
Chen MingJenn,
Yeh ChaoBin
Publication year - 2018
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22551
Subject(s) - niclosamide , chemistry , gene knockdown , cancer research , hepatocellular carcinoma , motility , western blot , cell growth , pharmacology , biology , microbiology and biotechnology , biochemistry , apoptosis , ecology , gene
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.