TY - JOUR T1 - Inhibition of Mammary Tumor Growth by a Novel Nontoxic Retinoid: Chemotherapeutic Evaluation of a C-Linked Analog of 4-HPR-Glucuronide JF - Anticancer Research JO - Anticancer Res SP - 2391 LP - 2398 VL - 25 IS - 3C AU - GALAL A. ALSHAFIE AU - JOEL R. WALKER AU - ROBERT W. CURLEY, JR. AU - MARGARET CLAGETT-DAME AU - MARGARET A. HIGHLAND AU - NIRCA J. NIEVES AU - LAURA A. STONEROCK AU - HUSSEIN ABOU-ISSA Y1 - 2005/05/01 UR - http://ar.iiarjournals.org/content/25/3C/2391.abstract N2 - Previous studies from our laboratory suggest that 4-HPROG, the O-glucuronide derivative of 4-HPR, has improved mammary cancer chemopreventive/ antitumor activities as well as reduced toxicity, as compared to 4-HPR. This O-linked glucuronide derivative is a substrate to the β-glucuronidase enzyme and may also undergo hydrolysis in vivo to the vitamin A metabolite, retinoic acid, that is toxic at high concentrations. In an effort to improve analog potency relative to its toxicity, the 4-HPROG's phenolic oxygen was replaced with a methylene group, thus preventing biological cleavage of the glucuronide moiety. The resulting C-linked analog, 4-HPR-C-glucuronide (4-HPRCG), cannot be hydrolyzed to 4-HPR. The results of this study show that 4-HPRCG is an effective chemotherapeutic agent that caused 49% regression of DMBA-induced mammary tumors in rats, while showing almost no side-effects that are often observed with other natural or synthetic retinoids, such as a reduction in blood retinol level, elevation in blood triglyceride (TG) level, and decrease in bone mineral content (BMC). These results suggest that 4-HPRCG should be considered as a better candidate for breast cancer treatment. ER -