Antitumor effects of glycosylated 4MU in a murine model of fibrosis associated-hepatocellular cancer

WEIZ G; MALVICINI M; RODRIGUEZ M; MAZZOLINI RIZZO G; BRECCIA JD; MOLEJON MI

Mar del Plata

Congreso; Reunión Anual de SOCIEDADES DE BIOCIENCIA; 2019

SAIC

Most drugs lack of systems that direct to the target tissues. In this way, a large part of drugs that remains in the bloodstream increases the secondary effects in the patients. The glycosylation of molecules is an interesting strategy for drug delivery to the specific target. The compound 4MU was described as inhibitor of the synthesis of hyaluronic acid and anticancer agent for hepatocellular carcinoma (HCC) associated with advanced fibrosis. In addition, treatment with $MU remodel tumor microenvironment resulting in a potent inhibition of tumor growth. The aim of this work was to evaluate the antitumoral effect of the glycosylated $MU. We modified 4MU, by the addition of a glycosidic moiety to obtain the product denominated 4MUR. Half maximal inhibitory concentration (IC50) of 4MU and 4MUR were determined on both, human and murine liver tumor cell lines (HUH 7 and Hepa 1.6, respectively) and compared the toxicity on normal human fibroblasts. The tumor cell lines were significantly more sensitive to the glycosylated compound 4MUR in a dose-dependent manner (p