Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells.

Abstract

Niclosamide, an oral antihelminthic drug, has been used to treat tapeworm infection for about 50 years. Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs. Recently, several groups have independently discovered that niclosamide is also active against cancer cells, but its precise mechanism of antitumor action is not fully understood. Evidence supports that niclosamide targets multiple signaling pathways (NF-κB, Wnt/β-catenin, Notch, ROS, mTORC1, and Stat3), most of which are closely involved with cancer stem cells. The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed. A method for synthesizing a phosphate pro-drug of niclosamide is provided. Given its potential antitumor activity, clinical trials for niclosamide and its derivatives are warranted for cancer treatment.

• Authors: Jing-Xuan Pan, Ke Ding, Cheng-Yan Wang
• Journal: Chinese journal of cancer (Chin J Cancer) Vol. 31 Issue 4 Pg. 178-84 (Apr 2012) ISSN: 1000-467X [Print] England
• PMID: 22237038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Multiprotein Complexes
• NF-kappa B
• Reactive Oxygen Species
• Receptors, Notch
• STAT3 Transcription Factor
• Niclosamide
• Mechanistic Target of Rapamycin Complex 1
• TOR Serine-Threonine Kinases

Topics

• Animals
• Antineoplastic Agents (pharmacokinetics, pharmacology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Humans
• Mechanistic Target of Rapamycin Complex 1
• Multiprotein Complexes (metabolism)
• NF-kappa B (metabolism)
• Neoplasm Metastasis
• Neoplasms (metabolism, pathology)
• Neoplastic Stem Cells (drug effects)
• Niclosamide (pharmacokinetics, pharmacology)
• Reactive Oxygen Species (metabolism)
• Receptors, Notch (metabolism)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Wnt Signaling Pathway (drug effects)