Dietary supplementation with silymarin inhibits 3,2'-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis in male F344 rats.
OBJECTIVE
Silymarin has been shown to be a potent anticarcinogenic agent. Here, we investigated the modifying effects of dietary feeding with a naturally occurring polyphenolic antioxidant flavonoid silymarin on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced prostatic carcinogenesis in male F344 rats.


METHODS
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 silymarin for 40 weeks, starting 1 week after the last dosing of DMAB. All of the rats were sacrificed 60 weeks after the start of the experiment. Histopathology and immunohistochemistry for proliferative cell nuclear antigen, cyclin D1, and apoptotic indices were done in the prostatic lesions, including invasive adenocarcinomas, intraepithelial neoplasms, 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 indices 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, dietary 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 and modification of cell proliferation.
Department of Oncologic Pathology, Kanazawa Medical University, Ishikawa, Japan. h-kohno@kanazawa-med.ac.jp
Hiroyuki
H
Kohno
Rikako
R
Suzuki
Shigeyuki
S
Sugie
Hiroyuki
H
Tsuda
Takuji
T
Tanaka
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000611:Aminobiphenyl Compounds; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D019938:Cyclin D1 / Q000032:analysis; D019587:Dietary Supplements; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D012838:Silymarin / Q000008:administration & dosage*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D000611:Aminobiphenyl Compounds; D000975:Antioxidants; D018809:Proliferating Cell Nuclear Antigen; D012838:Silymarin; C001042:2',3-dimethyl-4-aminobiphenyl; D019938:Cyclin D1