title: Cytotoxic and apoptotic effects of novel heterodinucleoside phosphates consisting of 5-fluorodeoxyuridine and Ara-C in human cancer cell lines.
abstract: In search for possible alternatives in the treatment of human malignancies we investigated several new heterodinucleoside phosphates consisting of 5-Fluorodeoxyuridine (5-FdUrd) and Arabinofuranosylcytosine (Ara-C). We show that all dimers tested inhibited the number of colonies of CCL228, CCL227, 5-FU resistant CCL227 and HT-29 human colon tumor cells with IC50 values ranging from 0.65 to 1 nM. Dimer # 2 inhibited the number of sensitive and Ara-C resistant H9 human lymphoma cells with IC50 values ranging from 200 to 230 nM. Since no significant difference in the cytotoxicity of the dimers could be observed between sensitive and resistant cells, these compounds might be used in the treatment of 5-FU and Ara-C resistant tumors.
authors.affiliation: Clinical Institute of Med. and Chem. Laboratory Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Saiko
authors.forename: W
authors.initials: W
authors.lastname: Bauer
authors.forename: Z
authors.initials: Z
authors.lastname: Horvath
authors.forename: T
authors.initials: T
authors.lastname: Hoechtl
authors.forename: M
authors.initials: M
authors.lastname: Grusch
authors.forename: C
authors.initials: C
authors.lastname: Illmer
authors.forename: S
authors.initials: S
authors.lastname: Madlener
authors.forename: G
authors.initials: G
authors.lastname: Krupitza
authors.forename: R M
authors.initials: RM
authors.lastname: Mader
authors.forename: H
authors.initials: H
authors.lastname: Schott
authors.forename: M
authors.initials: M
authors.lastname: Fritzer-Szekeres
authors.forename: T
authors.initials: T
authors.lastname: Szekeres
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D006690:Bisbenzimidazole / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004396:Coloring Agents / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology*; D019281:Dimerization; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008223:Lymphoma / Q000188:drug therapy; D011419:Propidium / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D004396:Coloring Agents; D015226:Dinucleoside Phosphates; D005456:Fluorescent Dyes; D003561:Cytarabine; D011419:Propidium; D006690:Bisbenzimidazole; D005472:Fluorouracil