Dietary sodium gluconate protects rats from large bowel cancer by stimulating butyrate production.
Butyrate has an antitumorigenic effect on colorectal cancer cell lines. Dietary sodium gluconate (GNA) promotes butyrate production in the large intestine. Accordingly, we examined the effect of dietary GNA on tumorigenesis in the large intestine in rats. Male Fisher-344 rats (n = 32) were divided into 4 groups: 2 diets (with or without 50 g GNA/kg basal diet) x 2 treatments (with or without carcinogen administration). Colonic tumors were induced by 3 intraperitoneal injections of azoxymethane (15 mg/kg body wt, 1 time/wk) and dietary deoxycholic acid (2 g/kg basal diet). The experiment was conducted for 33 wk except for a few rats. Ingestion of GNA increased cecal butyrate concentration at the end of experiment (P < 0.01). No tumor development occurred in the untreated groups. Ingestion of GNA decreased the incidence of tumors in rats administered the carcinogen (37.5 vs. 100%, P < 0.05). Ingestion of GNA also decreased the mean number of tumors per rat (0.5 +/- 0.8 vs. 2.8 +/- 1.5, P < 0.01). beta-Catenin accumulation and TdT-mediated dUTP nick end labeling (TUNEL) positive cells in tumors were histochemically examined. The results of this study suggested that the antitumorigenic effect of GNA may involve the stimulation of apoptosis through enhanced butyrate production in the large intestine.
Kameue
Chiyoko
C
Laboratory of Animal Science, Kyoto Prefectural University, Shimogamo, Kyoto 606-8522, Japan.
Tsukahara
Takamitsu
T
Yamada
Kouji
K
Koyama
Hironari
H
Iwasaki
Yoshie
Y
Nakayama
Keizo
K
Ushida
Kazunari
K
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000008:administration & dosage; D002087:Butyrates / Q000378:metabolism*; D002273:Carcinogens / Q000008:administration & dosage; D002432:Cecum / Q000737:chemistry / Q000473:pathology; D003106:Colon / Q000737:chemistry / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003598:Cytoskeletal Proteins / Q000032:analysis; D003840:Deoxycholic Acid / Q000008:administration & dosage; D004032:Diet; D005942:Gluconates / Q000008:administration & dosage*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007422:Intestines / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D015534:Trans-Activators / Q000032:analysis; D051176:beta Catenin
D002087:Butyrates; D002273:Carcinogens; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D005942:Gluconates; D015534:Trans-Activators; D051176:beta Catenin; D003840:Deoxycholic Acid; D001397:Azoxymethane; C030691:gluconic acid