Molecular mechanisms of niclosamide antitumor activity

Abstract

In this review the recent data regarding the antitumor activity of niclosamide and the molecular mechanisms of its antitumor activity are presented. Niclosamide has been used in the clinic for the treatment of intestinal parasite infections. In recent years in several screening investigations of various drugs and chemical compounds niclosamide was identified as a potential anticancer agent. Niclosamide not only inhibits the Wnt/b-catenin, mTORC1, STAT3, NF-kB and Notch signaling pathways, but also targets mitochondria in cancer cells to induce growth inhibition and apoptosis. A number of studies have established the anticancer activity of niclosamide in both in vitro and in vivo in xenotransplantation models using human tumors and immunodeficient mice. It is important that niclosamide is active not only against tumor cells but also cancer stem cells. Normal cells are resistant to niclosamide. The accumulated experimental data suggest niclosamide is a promising drug for the treatment of various types of cancer.

Evaluation of quantitative assays for the identification of direct signal transducer and activator of transcription 3 (STAT3) inhibitors

“…The increased potency of niclosamide in the cell-based ELISA suggests that niclosamide may also target other members upstream of STAT3, resulting in a greater impact on STAT3-DNA binding. This is further supported in the literature, as niclosamide has been investigated for its anticancer activity in additional signaling cascades many of which crosstalk with the STAT3 signaling pathway [39–42]. …”

Flavopiridol (Alvocidib), a Cyclin-dependent Kinases (CDKs) Inhibitor, Found Synergy Effects with Niclosamide in Cutaneous T-cell Lymphoma

“…Now it has found a new application in cancer therapy [ 29 ]. Its molecular mechanism has been thoroughly studied and occurs through targeting Wnt/β-catenin, mTOR, JAK/STAT3, NF-κB, and Notch pathways [ 32 ]. Based on our study, a higher dose FVP (240nM) impairs ion channel complexes of cancer patients likely contributed to the adverse effects that FVP recipients experienced in clinical trials.…”

Niclosamide, a Drug with Many (Re)purposes

“…These observed anticancer activities have been linked to niclosamide's ability to damage tumor cell mitochondria, induce apoptosis, inhibit tumor cell proliferation, and inhibit various aberrant tumor signaling pathways including Wnt/β‐catenin, mTORC1, STAT3, nuclear factor‐κB (NF‐κB) and Notch pathway (reviewed in detail by Moskaleva et al …”