We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The effect of N-acetylcysteine on the antitumor activity of ifosfamide.
- Authors
Chen, Nancy; Hanly, Lauren; Rieder, Michael; Yeger, Herman; Koren, Gideon
- Abstract
Ifosfamide-induced nephrotoxicity is a serious adverse effect in children undergoing chemotherapy. Our previous cell and rodent models have shown that the antioxidant N-acetylcysteine (NAC), used extensively as an antidote for acetaminophen poisoning, protects renal tubular cells from ifosfamide-induced nephrotoxicity at a clinically relevant concentration. For the use of NAC to be clinically relevant in preventing ifosfamide nephrotoxicity, we must ensure there is no effect of NAC on the antitumor activity of ifosfamide. Common pediatric tumors that are sensitive to ifosfamide, human neuroblastoma SK-N-BE(2) and rhabdomyosarcoma RD114-B cells, received either no pretreatment or pretreatment with 400 µmol/L of NAC, followed by concurrent treatment with NAC and either ifosfamide or the active agent ifosfamide mustard. Ifosfamide mustard significantly decreased the growth of both cancer cell lines in a dose-dependent manner ( p < 0.001). The different combined treatments of NAC alone, sodium 2-mercaptoethanesulfonate alone, or NAC plus sodium 2-mercaptoethanesulfonate did not significantly interfere with the tumor cytotoxic effect of ifosfamide mustard. These observations suggest that NAC may improve the risk/benefit ratio of ifosfamide by decreasing ifosfamide-induced nephrotoxicity without interfering with its antitumor effect in cancer cells clinically treated with ifosfamide.
- Subjects
ANTINEOPLASTIC agents; NEPHROTOXICOLOGY; DRUG side effects; ACETAMINOPHEN; TUMORS in children; CANCER cells; DOSE-response relationship in biochemistry
- Publication
Canadian Journal of Physiology & Pharmacology, 2011, Vol 89, Issue 5, p335
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/y11-028