title: Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest.
abstract: Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. In vitro cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. hanjini@snu.ac.kr.|WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea. hanjini@snu.ac.kr.
authors.forename: Han Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. ldydo@hanmail.net.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Lim
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. kgt486@snu.ac.kr.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Korea. kgt486@snu.ac.kr.
authors.forename: Gyoo Taik
authors.initials: GT
authors.lastname: Kwon
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. jihui6657@daum.net.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, Guangdong 523808, China. zn_huang@yahoo.com.
authors.forename: Zunnan
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. hyerim0715@hallym.ac.kr.
authors.forename: Hyerim
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Molecular Medicine, School of Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-799, Korea. with62@gachon.ac.kr.
authors.forename: Yoon Sin
authors.initials: YS
authors.lastname: Oh
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. yhkang@hallym.ac.kr.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea. kiwon@snu.ac.kr.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Korea. kiwon@snu.ac.kr.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN 55912, USA. zgdong@hi.umn.edu.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. jyoon@hallym.ac.kr.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Korea. jyoon@hallym.ac.kr.|Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea. jyoon@hallym.ac.kr.
authors.forename: Jung Han Yoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates; C031403:benzyl isothiocyanate
keywords: TRAMP; benzyl isothiocyanate; cell cycle arrest; prostate cancer development