Geranylgeranylacetone (GGA), an
isoprenoid compound, is an anti-
ulcer drug developed in Japan. GGA protects a variety of cells and tissues against numerous stresses via induction of
heat shock protein (HSP) 70, and it has recently been reported to protect mice from experimental
ulcerative colitis (UC). However, it is unknown whether GGA exhibits a preventive effect on UC-associated
neoplasia. In the present study, we evaluated the preventive effects of GGA on
colitis-related
carcinogenesis in the mouse colon. Mice were administered
1,2-dimethylhydrazine (
DMH) subcutaneously three times within a week, followed by 2 cycles of
dextran sulfate sodium (DSS) (each cycle, 3% DSS for 7 days and then distilled water for 14 days) and they were sacrificed 28 days after the completion of the 2 cycles. The mice were divided into the following groups according to the diet received during the experiment: group A, which received a standard diet and served as a disease control; group B, which received a diet mixed with 0.25% GGA; group C, which received a diet mixed with 0.5% GGA; group D, which received a diet mixed with 1.0% GGA; group E, which received a diet mixed with 2.0% GGA; and group F, which received a diet containing no agents, including DSS and served as a normal control. The incidence of
neoplasia was assessed. The expression of
inducible nitric oxide synthase (iNOS) and
8-hydroxy-2'-deoxyguanosine (8-OHdG) was also determined. In addition, the expression of HSP70 in the colon tissues was determined by immunohistochemistry and western blot analysis. The mean number of
tumors was 16.6, 11.0, 9.4, 5.8, 5.4 and 0 in groups A-F, respectively. GGA significantly suppressed the occurrence of
neoplasia in a dose-dependent manner. GGA treatment enhanced the expression of HSP70 and suppressed the oxidative damage in the background mucosa (i.e. lesion-free colon). These results suggest that GGA could be useful in the prevention of UC-associated
neoplasia.