Dietary feeding of dibenzoylmethane inhibits prostate cancer in transgenic adenocarcinoma of the mouse prostate model.
Dibenzoylmethane (DBM), a minor beta-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 G(2)-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.
Khor
Tin Oo
TO
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Yu
Siwang
S
Barve
Avanthika
A
Hao
Xingpei
X
Hong
Jin-Liern
JL
Lin
Wen
W
Foster
Barbara
B
Huang
Mou-Tuan
MT
Newmark
Harold L
HL
Kong
Ah-Ng
AN
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002453:Cell Cycle / Q000187:drug effects*; D047188:Chalcones / Q000008:administration & dosage*; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D019048:Prostatic Intraepithelial Neoplasia / Q000178:diet therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D047188:Chalcones; C061481:dibenzoylmethane