title: Protective effects of citrus nobiletin and auraptene in transgenic rats developing adenocarcinoma of the prostate (TRAP) and human prostate carcinoma cells.
abstract: Dietary phytochemicals, including nobiletin and auraptene, have been shown to exert inhibiting effects in several chemically induced carcinogenesis models. We here investigated the influence of nobiletin and auraptene on prostate carcinogenesis using transgenic rats developing adenocarcinoma of the prostate (TRAP) bearing the SV40 T antigen transgene under control of the probasin promoter and human prostate cancer cells. Starting at 5 weeks of age, male TRAP rats received powder diet containing 500 p.p.m. nobiletin or auraptene, or the basal diet for 15 weeks and then were sacrificed for analysis of serum testosterone levels and histological changes. The body and relative prostate weights and serum testosterone levels did not differ among the groups. Since all animals developed prostate carcinomas, these were semiquantitatively measured and expressed as relative areas of prostate epithelial cells. Nobiletin caused significant reduction in the ventral (P<0.01), lateral (P<0.001) and dorsal (P<0.05) prostate lobes, while decreasing high grade lesions (P<0.05) in the ventral and lateral lobes. Feeding of auraptene also effectively reduced the epithelial component (P<0.05) and high grade lesions (P<0.05), in the lateral prostate. A further experiment demonstrated that growth of androgen sensitive LNCaP and androgen insensitive DU145 and PC3 human prostate cancer cells, was suppressed by both nobiletin and to a lesser extent auraptene in a dose-dependent manner, with significant increase in apoptosis. In conclusion, these compounds, particularly nobiletin, may be valuable for prostate cancer prevention.
authors.affiliation: 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.
authors.forename: MingXi
authors.initials: M
authors.lastname: Tang
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Naomi
authors.initials: N
authors.lastname: Hokaiwado
authors.forename: Azman
authors.initials: A
authors.lastname: Seeni
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000494:pharmacology*; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D014674:Plant Proteins, Dietary / Q000494:pharmacology; D011230:Precancerous Conditions; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D003374:Coumarins; D047309:Flavones; D014674:Plant Proteins, Dietary; D020011:Protective Agents; C008661:nobiletin; C105832:aurapten