Dietary butyrate inhibits NMU-induced mammary cancer in rats

Nutr Cancer. 2000;36(2):217-23. doi: 10.1207/S15327914NC3602_11.

Abstract

Butyrate has been proposed as an antineoplastic agent, leading to the inhibition of tumorigenesis. The purpose of this study was to examine butyrate, supplied as tributyrin (Tbn) or as a natural component of anhydrous milk fat (AMF), on the development of nitrosomethylurea-induced mammary tumors in female Sprague-Dawley rats. Diets were 1) semipurified rodent diet (AIN-93) with high fat [20% sunflower seed oil (SSO), control], 2) SSO diet with Tbn added at 1%, 3) SSO diet with Tbn added at 3%, and 4) 19% AMF with 1% SSO diet, which contained butyrate equivalent to the 1% Tbn diet. These diets were fed ad libitum from weaning at 21 days of age, and at 24 days of age each rat was injected with nitrosomethylurea (50 mg/kg body wt i.p.). At any one period, there was a relative risk increase of 88% (p < 0.05) that rats in the SSO diet group would develop a mammary tumor compared with those in the AMF diet group. The addition of 1% and 3% Tbn to SSO diets reduced the tumor incidence by 20% and 52%, respectively, in comparison to SSO alone (p < 0.05). There was a linear inverse relationship between Tbn concentration and rats developing a tumor. From 89 days to the end of the experiment, rats fed the diet containing 3% Tbn showed a significantly lower multiplicity of palpable tumors (50% less at Day 118, p < 0.05) than SSO-fed rats. These results indicate that although the AMF diet was effective, particularly early in reducing mammary tumorigenesis, the 3% Tbn diet produced a sustained reduction of tumor multiplicity relative to the control (SSO) group. An inhibitory influence of butyrate on mammary tumorigenesis against a background of high polyunsaturated fat diet has been demonstrated in this animal model of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents
  • Animal Feed
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Butyrates / administration & dosage
  • Butyrates / therapeutic use*
  • Dietary Fats / administration & dosage*
  • Dietary Fats / analysis
  • Disease Models, Animal
  • Female
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / prevention & control*
  • Methylnitrosourea
  • Milk / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Triglycerides / administration & dosage

Substances

  • Alkylating Agents
  • Antineoplastic Agents
  • Butyrates
  • Dietary Fats
  • Triglycerides
  • Methylnitrosourea
  • tributyrin