Monday, July 25, 2011

Agent used to treat tapeworm infection inhibits colon cancer metastasis

Agent used to treat tapeworm infection inhibits colon cancer metastasis Elvira Manzano Niclosamide, an agent which has been around for more than half a century and which is approved for the treatment of intestinal parasite infections from tapeworms, may also be effective against colon cancer metastasis, new research suggests. Scientist Professor Ulrike Stein and colleagues from the Experimental and Clinical Research Center at Charité University Medicine at the Max Delbrück-Center for Molecular Medicine, Berlin, Germany, in collaboration with Professor Robert H. Shoemaker of the National Cancer Institute (NCI) in Frederick, Maryland, US, made the discovery while screening a library of 1,280 compounds for their ability to block the S100A4/metastasin gene, which can trigger colon cancer metastasis. Using high-throughput screening, niclosamide was identified as an S100A4 transcription inhibitor and found to efficiently inhibit the β-catenin-driven expression of the S100A4/metastasin gene both in mice and in cell culture. [J Natl Cancer Inst 2011; 103(12)] S100A4, a calcium binding protein originally identified as metastasin 1 (MTS1), is overexpressed in colon cancer and can initiate metastasis. Overexpression of this gene is also associated with tumor aggressiveness and poor survival in patients. Five years ago, Stein, working with Professor Peter Schlag, of the Charité Comprehensive Cancer Center, Charité University Medicine, in Berlin, Germany, and Professor Walter Birchmeier from MDC, showed how this gene is regulated. They found that the β-catenin gene, when mutant, activates the S100A4 gene, thus triggering colon cancer metastasis. In their latest studies, treatment with niclosamide significantly reduced liver metastasis formation in mice with xenografted intrasplenic tumors compared with controls (P<0.01). More importantly, inhibition of metastasis was still evident 26 days after discontinuation of niclosamide and overall survival was significantly higher in the active treatment group (P=0.001). In vitro, niclosamide-treated colon cancer cells showed reduced S100A4 mRNA and protein levels. The drug also inhibited S100A4-induced migration, invasion, proliferation and colony formation of colon cancers. The researchers said the new anti-metastatic function of niclosamide bears great potential for the treatment and prevention of colon cancer metastasis. Colon cancer is one of the most frequent causes of cancer death worldwide. Despite intensive healthcare programs for early diagnosis, many patients are still diagnosed at an advanced stage of the disease. In Germany alone, about 73,000 new cases of colon cancer are being diagnosed each year, with only about half of these patients cured. In patients with metastatic colon cancer, the 5-year survival rate is only about 10 percent.

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