Modulation of myogenic differentiation in a human rhabdomyosarcoma cell line by a new derivative of 5-fluorouracil (QF-3602)

The in vitro study of mechanisms involved in drug-induced maturation has ma de it possible to use differentiation-based therapy in clinical practice. T he goal of this new therapy is the development of specific agents to induce cancer cells to stop proliferating and express characteristics of normal c ells. Recently, by structural modifications of 5-fluorouracil (5-FU), we sy nthesized a new pyrimidine acyclonucleoside-like compound, 1-{[3-(3-chloro- 2-hydroxypropoxy)-1-methoxy]propyl}-5-fluorouracil (QF-3602), which showed in rhabdomyosarcoma cells a low toxicity and time-dependent growth inhibiti on. In this work, we compared the degree of myogenic differentiation of RE rhabdomyosarcoma (RMS) cells after treatment with QF-3602 and 5-FU, Scannin g and transmission electron microscopy (SEM and TEM) and immunocytochemical analyses showed that QF-3602 induced the appearance of myofilaments along the myotube-like giant RD cells, an increase in fibronectin and a decrease in vimentin expression, In contrast, only minor changes were observed with 5-FU, Moreover, polymerase chain reaction (PCR) analyses showed that QF-360 2 did not induce overexpression of the mdr I gene, a resistance mechanism t hat frequently appears in classical cytotoxic therapy in these tumors. Comp ounds obtained by structural modifications of 5-FU may be useful in differe ntiation therapy as a new approach to the treatment of 5-FU may be useful i n differentiation therapy as a new approach to the treatment of RMS.