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
1997
Abstract A series of new 5FU acyclonucleoside analogues has been synthesized and tested for their in vitro cytotoxicity versus HT-29 colon carcinoma. The only active compound is 14 , which is 8-fold less active than 5-fluorouracil. The rest of the newly prepared compounds showed no significant activity. We selected 14 as the drug in the treatment of an human embryonal cell line RD derived from rhabdomyosarcoma. Such treatment caused time-dependent growth inhibition. Interestingly, RD cells treated with 14 at a concentration of 90 μM for 6 days showed phenotypic differentiation, with increased expression of desmin, α-actinin and tropomyosin. We conclude that exposure of this human embryonal rhabdomyosarcoma cell line to a 90 μM concentration released the neoplastic cells from their blockade, allowing them to recover normal myogenic development.
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