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

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.

Estrogen receptor β regulates epithelial cellular differentiation in the mouse ventral prostate

“…Ligand-binding studies have shown that ER␤ exhibits a 40-fold higher affinity for genistein than does ER␣, suggesting that this compound may act through ER␤-signaling pathways (32). In the rat prostate, isoflavones up-regulate heat shock protein HSP-27 and inhibit progression of PIN to adenocarcinoma (33). Because ER␤ is the only ER in the prostate, and heat shock protein HSP-27 is known to be induced by estrogen (34), it is tempting to speculate that isoflavones might act through ER␤.…”

Genistein Induces the p21WAF1/CIP1 and p16INK4a Tumor Suppressor Genes in Prostate Cancer Cells by Epigenetic Mechanisms Involving Active Chromatin Modification

“…Prepubertal exposure to soy or genistein reduced mammary carcinogenesis in rats treated with carcinogens, possibly by modulating the development of the mammary end buds (2). Various soy products containing genistein have been found to inhibit the growth of transplanted human prostate carcinoma, reduce the incidence of poorly differentiated prostate adenocarcinoma in a transgenic mouse model, and inhibit 2-amino-1-methyl-6-phenylimidazo [4,5]pyridine-induced rat prostate carcinogenesis (3). Carcinogenesis or metastasis in the stomach, colon, bladder, and lung is also inhibited by genistein and related isoflavones (4)(5)(6).…”

Regulation of Minichromosome Maintenance Gene Family by MicroRNA-1296 and Genistein in Prostate Cancer

“…Various soy products containing genistein have been found to inhibit the growth of transplanted human prostate carcinoma, reduce the incidence of poorly differentiated prostate adenocarcinoma in a transgenic mouse model, and inhibit 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridineinduced rat prostate cancer (36). Carcinogenesis or metastasis to the stomach, colon, bladder, and lung is also inhibited by genistein and related isoflavones (37)(38)(39).…”