Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

Carcinogenesis. 2004 Mar;25(3):381-7. doi: 10.1093/carcin/bgh031. Epub 2003 Dec 4.

Abstract

Intake of isoflavones derived from soybean products may impact on prostate cancer risk. Here we evaluated the effects of Fujiflavone, a commercial isoflavone supplement, on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant heterocyclic amine in cooked meat. F344 male rats were given intragastric administrations of PhIP at the dose of 200 mg/kg twice weekly for 10 weeks. The rats subsequently fed a diet containing 0.25% Fujiflavone showed a significantly lower incidence of prostate carcinomas than those fed a soy-free diet. Interestingly fewer carcinomas but more foci of prostatic intra-epithelial neoplasia (PIN) were observed in the Fujiflavone group although the sum of the two lesions was not altered by Fujiflavone treatment. cDNA array analyses confirmed by semi-quantitative reverse transcription polymerase chain reactions (RT-PCR) revealed Fujiflavone to alter gene expression of ornithine decarboxylase (ODC), prothymosin alpha (PTA) in the rat prostate. No modification of PhIP-induced colon carcinogenesis was evident, except for increased multiplicity of aberrant crypt foci >4 crypts in size. These results indicate that a commercial isoflavone supplement can inhibit PhIP-induced rat prostate carcinogenesis without any adverse effects, possibly by inhibiting progression of PIN to carcinoma, and that down-regulation of ODC and PTA could be related to the underlying mechanisms. Thus, intake of dietary isoflavones can be promising for prevention of human prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Body Weight
  • Carcinogens / pharmacology*
  • Colonic Neoplasms / drug therapy
  • Imidazoles / pharmacology*
  • Isoflavones / pharmacology*
  • Male
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / etiology
  • Rats

Substances

  • Antineoplastic Agents
  • Carcinogens
  • Imidazoles
  • Isoflavones
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine