Edward E Knaus
Canada
Research Article
Dual-acting 5-Fluorodeoxyuridine (FUdR) Prodrugs: Cell Death Induced by 3’-O-retinoyl-5-fluoro-2’-deoxyuridine and 5’-O-[bis(2,2,2,-trichloroethyl)phosphoryl-3’-O-butanoyl]-5-fluoro-2’-deoxyuridine
Author(s): Zuping Xia, Edward E Knaus and Leonard I WiebeZuping Xia, Edward E Knaus and Leonard I Wiebe
Several novel 5-fluoro-2?-deoxyuridine (FUdR) prodrugs with postulated dual mechanisms of anticancer activity based on nucleoside cytotoxicity and cell differentiation induced by retinoic acid/butyric acid have been reported. The O-retinoyl- and O-butanoyl- esters of FUdR were reported to be more potent and had broader anticancer spectra than either FUdR or 5-fluorouracil (FU) against a bank of human cancer cell lines. The induction of necrosis or apoptosis in HL-60 cells by 3?-O-retinoyl-5-fluoro-2?-deoxyuridine (RFUdR) and the masked butyryl ester nucleotide, 5?-O-bis(trichloroethyl)phosphoryl-3?-O-butanoyl-5-fluoro-2?-deoxyuridine (BTCEP-BFUdR), is now reported. Apoptosis was the major pathway of HL-60 cell death caused by RFUdR (1 � 10-5 M), independent of the exposure time. In contrast, apoptosis and necrosis were equally evident after exposure to BTCEP-BFUdR (1 � 10-5 M) for 48 h, .. View More»
DOI:
10.4172/2161-1459.1000143