TY - JOUR
T1 - Chitin or chitin-like glycans as targets for late-term cancer chemoprevention
AU - Wattenberg, Lee W.
AU - Patterson, Steven
AU - Antonides, Jennifer D.
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
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U2 - 10.1158/1940-6207.CAPR-09-0230
DO - 10.1158/1940-6207.CAPR-09-0230
M3 - Comment/debate
C2 - 21149328
AN - SCOPUS:78650389020
SN - 1940-6207
VL - 3
SP - 1519
EP - 1522
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 12
ER -