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Chitin or Chitin-like Glycans as Targets for Late-term Cancer Chemoprevention
A consistent observation in studies of carcinogenesis is that some glycans are expressed differently in cancer cells than in normal cells. A well-known example is the aberrant β1-6 N-acetyl-D-glucosamine branching associated with metastasis and poor prognosis in many cancers. This commentary proposes that, although not found in normal mammalian cells, a chitin (β-1,4-linked N-acetyl-D-glucosamine) or a chitin-like polysaccharide (e.g. hyaluronan) may exist as a cancer-associated glycan, which can be targeted by the novel pyrimidine nucleotide derivative SP-1015 (designed as a chitin synthase inhibitor). Preliminary chemoprevention data of our group showed SP-1015 in the diet can inhibit benzo(a)pyrene-induced neoplasia in the forestomach of female A/J mice, and of importance, this activity occurred at late stages in carcinogenesis. While no effect was seen in the murine lung, this may be due to the low bioavailability of the compound. A different route of administration (e.g. inhalation of an aerosol) may have potential to inhibit pulmonary carcinogenesis. We hypothesize that inhibitors of chitin or chitin-like glycan formation may be effective chemopreventive agents and suggest that further work is needed to study these novel targets for cancer prevention.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058766/
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