History and mechanism of action of niclosamide
Niclosamide is listed on the WHO list of essential medications and
chewable tablets have been approved for use as an anti-helminthic agent
for cestode (tapeworm) infections for over 40 years (Andrews, Thyssen,
& Lorke, 1982). Animal studies have shown that niclosamide, has no
mutagenic, oncogenic or embryotoxic activity. In humans it is rapidly
eliminated by the kidneys with no cumulative toxic effects (Andrews et
al., 1982). Structurally, niclosamide belongs to a large group of
lipophilic, weakly acidic molecules called salicylanilides, a derivative
of salicylic acid (Pearson & Hewlett, 1985). Niclosamide inhibits
oxidative phosphorylation and stimulates ATP activity in the
mitochondria of cestodes, killing both the scolex and the proximal
segments of the tapeworm (Al-Hadiya, 2005; Weinbach & Garbus, 1969). In
humans, it has been shown to affect several signal transduction pathways
such as Wnt/β-catenin, mechanistic target of rapamycin (mTOR) complex 1
(mTORC1), signal transducer and activator of transcription 3 (STAT-3),
nuclear factor-kappa B (NF-κB), Notch and NS2B-NS3, all indicating its
potential to treat conditions such as cancer (summarised in Table 1),
chronic medical diseases, and bacterial and viral infections.