Dietary supplementation with silymarin inhibits 3,2′-dimethyl-4- aminobiphenyl-induced prostate carcinogenesis in male F344 rats

Abstract

Purpose: Silymarin has been shown to be a potent anticarcinogenic agent. Here we investigated the modifying effects of dietery feeding with a naturally occurring polyphenolic antioxidant flavonoid silymarin on 3,2′-dimethyl-4- aminobiphenyl (DMAB)-Induced prostatic carcinogenesis in male F344 rats. Experimental Design: Male F344 rats were given s.c. injections of DMAB (25 mg/kg body weight) every other week for 20 weeks. They also received the experimental diet containing 100 or 500 ppm silymain for 20 weeks, starting 1 week after the last dosing of DMAB. All of the rats were sacrificed 80 weeks after the start of the experiment. Histopathology and immunohistochemistry for proliferative cell nuclear antingen, cyclin D1, and apoptotic indices were done in the prostatic lesions, including invasive adenocarcinomas, intraepithelial neoplasmas, and nonlesional glands. Results: Dietary feeding with 500 ppm silymarin significantly inhibited the incidence of prostatic adenocarcinoma when compared with the DMAB-alone group (17.6% versus 50.0% P < 0.05). The proliferative cell nuclear antigen- and cyclin D1 - positive in adenocarcinomas, prostatic intraepithelial neoplasm, and nonlesional glands in rats treated with DMAB and silymarin were slightly lower than that of the DMAB-alone group. Also diatary administration of silymarin increased apoptotic index in prostatic adenocarcinoma by measuring immunohistochemically positive nuclei for ssDNA. Conclusions: Our results indicate that silymarin exerts chemopreventive ability against chemically induced prostatic carcinogenesis through apoptosis induction modification of cell proliferation. © 2005 American Association for Cancer Research.