Suppressive Effects of Dietary Genistin and Daidzin on Rat Prostate Carcinogenesis

Abstract

High intake of phytoestrogens through soybeans and their products is thought to be associated with low incidences of prostate and/or breast cancer in Asian countries. Possible chemopreventive effects of genistin or daidzin on rat prostate carcinogenesis were therefore investigated. Male F344 rats were given 10 biweekly subcutaneous injections of 3,2′ ′ ′ ′-dimethyl-4-aminobiphenyl (DMAB) and then either genistin or daidzin in the diet at a concentration of 0.1% for 40 weeks. Other groups of rats given DMAB were treated with genistin or daidzin together with a high dose of testosterone propionate (TP). Both genistin and daidzin reduced the numbers of ventral prostate carcinomas (P < < < <0.05), with a tendency for decrease in incidence. Invasive carcinomas which developed in the anterior prostate and seminal vesicles with TP were, however, not influenced by the two isoflavones. Thus, the present data suggest that genistin and daidzin possess anti-cancer effects at relatively early stages of prostate cancer development, providing experimental support for epidemiological findings. Key words: Rats -DMAB -Prostate carcinogenesis -Genistin -DaidzinWhile prostate cancer is the most common internal neoplasm and the second leading cause of cancer death in men in the United States, 1) mortality in Japan from this cause is only two-ninths of that in the United States. 2)Intake of large amounts of soybeans and their products rich in isoflavones, such as genistin and daidzin, is believed to play a role in this difference.3) The daily consumption of isoflavones in the diet by Japanese people is estimated to be approximately 18 mg, 4) and geometric mean plasma individual isoflavonoid concentrations are 7 to 110 times higher in Japanese than in Finnish men. 5)Animal studies have shown that these two isoflavones inhibit carcinogen-induced tumors of mammary glands 6,7) and skin. 8) Recently, Onozawa et al. 9) reported that a soybean isoflavone mixture consisting of 74% genistein and 21% daidzein suppressed the development of invasive carcinomas of the rat prostate/seminal vesicles.In vitro studies have revealed that genistein is an inhibitor of protein tyrosine kinase, which modulates several cellular activities and plays an important role in cell proliferation and cell transformation, 10,11) and also inhibits mammalian DNA topoisomerase II 12) as well as angiogenesis. 13)Genistein and daidzein both have a heterocyclic phenol structure that closely resembles estrogens and enables them to bind to estrogen receptors and to exert weak estrogenic activities. 14-17) Normally soybeans and their products contain glycosides of the isoflavones, genistin and daidzin, and these are deglycosylated by intestinal β-glucuronidase to afford the active forms, genistein and daidzein. We have established an animal model of prostate cancer using 3,2′-dimethyl-4-aminobiphenyl (DMAB). 18,19) This carcinogen induces non-invasive prostate adenocarcinomas limited to the ventral lobe, but invasive and metastasizing adenocarcinomas originating from the d...

Pro-apoptotic effect and cytotoxicity of genistein and genistin in human ovarian cancer SK-OV-3 cells

“…Although the pro-apoptotic effects of Life Sciences 80 (2007) (Linford et al, 2001;Linford and Dorsa, 2002;Choi and Lee, 2004). Genistin-induced cytotoxicity has not yet been reported, but accounts of some studies in vitro have suggested that genistin has biological activity (Kato et al, 2000;Allred et al, 2001). In the present study, we investigated and compared the possible pro-apoptotic effects of genistin and genistein in human ovarian SK-OV-3 cells.…”

Uterine phenotype of young adult rats exposed to dietary soy or genistein during development

“…However, the popular association of GEN and soyfoods is not entirely accurate; while native soy proteins have predominantly the isoflavone conjugate genistin, which undergoes intestinal metabolism to the aglycone and other molecular forms upon ingestion, GEN available in health food stores exists solely as the aglycone component. Moreover, soy proteins are also a rich source of the isoflavone daidzen, which has been demonstrated to exhibit biological effects in animal models in vivo and carcinoma cells in vitro [17,23,24].…”

How isoflavone levels in common rodent diets can interfere with the value of animal models and with experimental results

“…Kato et al (2000) investigated the effects of dietary genistein and daidzein on prostate cancer induction. In groups of male rats, prostate cancer was induced via injection with the carcinogen DMBA.…”