title: Effects of WR-2721 (amifostine) and its metabolite WR-1065 on the antiproliferative activity of chemotherapeutic agents on neuroblastoma cells in vitro.
abstract: Amifostine (WR-2721) is currently being investigated as a potential protector of normal tissues during chemotherapy in adult and pediatric cancer patients. The marked reduction of bone marrow and renal toxicity by amifostine is well documented, but data are lacking whether the anticancer activity of cytostatic drugs is also preserved in neuroblastoma as the second most common pediatric malignancy. We investigated the cytotoxic effect of six drugs on two neuroblastoma cells lines chosen for their presence or absence of N-myc amplification and PGY1 overexpression: IMR-5 (N-myc 25 x, PGY1-negative), CHP-100 (N-myc 1x, PGY1-positive) in vitro in the presence and absence of WR-2721 and its active metabolite WR-1065 using the monolayer proliferation assay. Doxorubicin, vincristine, etoposide, cisplatin, 4-hydroperoxycyclophosphamide and 4-hydroperoxyifosfamide were equally cytotoxic with and without preincubation of WR-2721 (14 mM) or WR-1065 (40 microM) as shown by virtually identical dose-response curves and ID50 values. We conclude that WR-2721 and WR-1065 did not reduce the cytostatic activity of six commonly used drugs on neuroblastoma cell lines in vitro.
authors.affiliation: Department of Pediatric Hematology and Oncology, Children's Hospital, University of Cologne, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Fulda
authors.forename: W
authors.initials: W
authors.lastname: Oster
authors.forename: F
authors.initials: F
authors.lastname: Berthold
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008624:Mercaptoethylamines / Q000494:pharmacology*; D009447:Neuroblastoma / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D004999:Amifostine