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Dietary Feeding of Dibenzoylmethane Inhibits Prostate Cancer in Transgenic Adenocarcinoma of the Mouse Prostate Model

Departments of ¹ Pharmaceutics and ² Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, and ³ Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Ah-Ng Kong, Department of Pharmaceutics, Ernest-Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854. Phone: 732-445-3831, ext. 228; Fax: 732-445-3134; E-mail: KongT{at}rci.rutgers.edu.

Key Words: dibenzoylmethane • prostate cancer • TRAMP mice

Dibenzoylmethane (DBM), a minor β-diketone constituent of licorice, has been shown to exhibit antineoplastic effects in prostate cancer cell lines by induction of cell cycle arrest and regulation of androgen receptor expression. In the present study, we investigated the in vitro and in vivo efficacy of DBM using TRAMP-C1 cell lines and TRAMP mice. DBM was found to arrest TRAMP-C1 cells at G₂-M phase of cell cycle and suppressed phosphorylated retinoblastoma, cyclin D1, and cyclin A. Importantly, DBM was found to be equally effective in suppression of prostate tumor progression in TRAMP mice. At 8 or 12 weeks of age, mice were fed control or 1% DBM-supplemented diets until 24 weeks of age. Our results show that DBM-fed groups had a lower incidence of palpable tumor and high-grade prostatic intraepithelial neoplasia. Subsequent mechanistic studies show that the expression of phosphorylated retinoblastoma, c-myc, cyclin D1, cyclin A, phosphorylated Akt, phosphorylated PDK-1, and phosphorylated S6 was significantly reduced by DBM. Our findings suggest that DBM blocks the growth and progression of prostate cancer in TRAMP mice via modulation of tumor cell cycle regulation and therefore merits its consideration for future clinical intervention of human prostate cancer. [Cancer Res 2009;69(17):7096–102]