Chemical modifications on the acyclic moiety of 3-(2-hydroxyethoxy)-1-alkoxypropyl nucleobases. 2. Differentiation and growth inhibition in rhabdomyosarcoma cells after exposure to a novel 5-fluorouracil acyclonucleoside

✍ Scribed by Jose A. Gómez; Joaquín Campos; Juan A. Marchal; María A. Trujillo; Consolación Melguizo; José Prados; Miguel A. Gallo; Antonia Aránega; Antonio Espinosa

• Publisher: Elsevier Science
• Year: 1997
• Tongue: French
• Weight: 1023 KB
• Volume: 53
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(97)00415-8

✦ Synopsis

A series of new 5FU aeyclonucleoside analogues has been synthesized and tested for thor in vitro cytotoxicity versus ttT-29 colon carcinonm. The only active compound is I-{ [3-(3-eloro-2-hydroxypmpoxy)-lmethoxy]propoxy}-5-flutmmtadl 14, which is 8-fold less active than 5-fluorouracE The rest of the newly prepared compounds showed no si~ifu~t activity. We selected 14 as the drag in the treatment of an human embryonal cell line RD derived from rlmlxlomyosarcoma. Such treatmem caused time-depondent growth inhibition. Interestingly, RD cells Ire~_t~ with 14 at a concentration ofg0 tim for 6 days showed pheaotypic differentiation, with increased expression of d~m/n~ a-actlnln and tropomyosin. We conclude that exposure of this human embryonal rhabdomyosarcoma cell line to a 90 I~M concoatration released the neoplastic cells from their blockade, allowing them to recover normal myogeaic development.