Inhibitory effects of soy isoflavones on rat prostate carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).
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.
Hikosaka
Atsuya
A
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. atsuhiko@med.nagoya-cu.ac.jp
Asamoto
Makoto
M
Hokaiwado
Naomi
N
Kato
Koji
K
Kuzutani
Kazuya
K
Kohri
Kenjiro
K
Shirai
Tomoyuki
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight; D002273:Carcinogens / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000209:etiology; D051381:Rats
D000970:Antineoplastic Agents; D002273:Carcinogens; D007093:Imidazoles; D007529:Isoflavones; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine