title: Geranylgeranylacetone suppresses colitis‑related mouse colon carcinogenesis.
abstract: 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.
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Takuya
authors: T
authors: Inoue
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Naoki
authors: N
authors: Yorifuji
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Munetaka
authors: M
authors: Iguchi
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Kaori
authors: K
authors: Fujiwara
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Kazuki
authors: K
authors: Kakimoto
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Sadaharu
authors: S
authors: Nouda
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Toshihiko
authors: T
authors: Okada
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Ken
authors: K
authors: Kawakami
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Yosuke
authors: Y
authors: Abe
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Toshihisa
authors: T
authors: Takeuchi
authors: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Kazuhide
authors: K
authors: Higuchi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004224:Diterpenes / Q000627:therapeutic use*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D003849:Deoxyguanosine; C031049:geranylgeranylacetone