Effects of WR-2721 (amifostine) and its metabolite WR-1065 on the antiproliferative activity of chemotherapeutic agents on neuroblastoma cells in vitro

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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 cytostatlc drugs is also preserved in neuroblastoma as the second most common pediatric malignancy. We investigated the cytotoxic effect of six drugs on two neuroblastoma cell lines chosen for their presence or absence of N-myc amplification and PGY1 overexpression: IMR-5 (N-myc 25x, 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-hydroperoxycyclophosphamlde and 4- hydroperoxyifosfamide were equally cytotoxic with and without preincubation of WR-2721 (14 mM) or WR-1065 (40µM) 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.

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