Modulation of Myogenic Differentiation in a Human Rhabdomyosarcoma Cell Line by a New Derivative of 5-Fluorouracil (QF-3602) |
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Authors: | Juan Antonio Marchal,Consolació n Melguizo,Jose Prados,Amelia Eva Ará nega,Jose Antonio Gó mez,Joaquin Campos,Miguel Angel Gallo,Antonio Espinosa,Nicolo Arena,Antonia Ará nega |
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Affiliation: | Departamento de Ciencias de la Salud, Facultad de Ciencias Experimentales, Universidad de Jaén, 23071 Jaén, Spain;Departamento de Ciencias de la Salud, Universidad de Almeria, 04120 Almeria, Spain;Departamento de Quimica Orgánica, Facultad de Farmacia, Universidad de Granada, 18071 Granada, Spain;Departamento de Ciencias Morfológicas, Facultad de Medicina, Universidad de Granada, 18071 Granada, Spain;Istituto di Istologia, Facultádi Medicina e Chirurgia, Universitádi Sassari, 07100 Sassari, Italy |
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Abstract: | The in vitro study of mechanisms involved in drug-induced maturation has made it possible to use differentiation-based therapy in clinical practice. The goal of this new therapy is the development of specific agents to induce cancer cells to stop proliferating and express characteristics of normal cells. Recently, by structural modifications of 5-fluorouracil (5-FU), we synthesized 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 inhibition. In this work, we compared the degree of myogenic differentiation of RD rhabdomyosarcoma (RMS) cells after treatment with QF-3602 and 5-FU. Scanning 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-3602 did not induce overexpression of the mdr 1 gene, a resistance mechanism that frequently appears in classical cytotoxic therapy in these tumors. Compounds obtained by structural modifications of 5-FU may be useful in differentiation therapy as a new approach to the treatment of RMS. |
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Keywords: | Differentiation therapy Acyclonucleoside prodrugs Fibronectin Vimentin Rhabdomyosarcoma |
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