Dietary supplement 4-methylumbelliferone: an effective chemopreventive and therapeutic agent for prostate cancer.

ABSTRACT: Prevention and treatment of advanced prostate cancer (PCa) by a nontoxic agent can improve outcome, while maintaining quality of life. 4-methylumbelliferone (4-MU) is a dietary supplement that inhibits hyaluronic acid (HA) synthesis. We evaluated the chemopreventive and therapeutic efficacy and mechanism of action of 4-MU. TRAMP mice (7-28 per group) were gavaged with 4-MU (450mg/kg/day) in a stage-specific treatment design (8-28, 12-28, 22-28 weeks). Efficacy of 4-MU (200-450mg/kg/day) was also evaluated in the PC3-ML/Luc(+) intracardiac injection and DU145 subcutaneous models. PCa cells and tissues were analyzed for HA and Phosphoinositide 3-kinase (PI-3K)/Akt signaling and apoptosis effectors. HA add-back and myristoylated Akt (mAkt) overexpression studies evaluated the mechanism of act

SUBMITTER: Yates TJ 

PROVIDER: S-EPMC4554252 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature