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

Marchal Corrales, Juan Antonio and Melguizo, Consolacion and Prados Salazar, José Carlos and Aranega, Amelia Eva and Gómez, José Antonio and Campos Rosa, Joaquin and Gallo, Miguel Angel and Espinosa, Antonio and Arena, Nicola and Aranega Jiménez, Antonia (2000) Modulation of myogenic differentiation in a human rhabdomyosarcoma cell line by a new derivative of 5-fluorouracil (QF-3602). Cancer Science, Vol. 91 (9), p. 934-940. eISSN 1349-7006. Article.

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DOI: 10.1111/j.1349-7006.2000.tb01037.x

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.

Item Type:Article
ID Code:1331
Status:Published
Refereed:Yes
Uncontrolled Keywords:Differentiation therapy, acyclonucleoside prodrugs, fibronectin, vimentin, rhabdomyosarcoma
Subjects:Area 06 - Scienze mediche > MED/03 Genetica medica
Divisions:001 Università di Sassari > 03 Istituti > Anatomia patologica
Publisher:Japanese Cancer Association
eISSN:1349-7006
Deposited On:18 Aug 2009 10:04

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