Preclinical high-dose acetaminophen with N -acetylcysteine rescue enhances the efficacy of cisplatin chemotherapy in atypical teratoid rhabdoid tumors

摘要: Background Atypical teratoid rhabdoid tumors (AT-RT) are pediatric of the central nervous system with limited treatment options and poor survival rate. We investigated whether enhancing chemotherapy toxicity by depleting intracellular glutathione (GSH; a key molecule in cisplatin resistance) high dose acetaminophen (AAP), may improve therapeutic efficacy AT-RT vitro. Procedure BT16 (cisplatin-resistant) BT12 (cisplatin-sensitive) cell lines were treated combinations AAP, cisplatin, anti-oxidant N-acetylcysteine (NAC). Cell viability, GSH peroxide concentrations, mitochondrial damage, apoptosis evaluated vitro. Results AAP enhanced cytotoxicity cisplatin-resistant BT16 cells but not cisplatin-sensitive cells. Baseline levels elevated compared to cells, AAP decreased greater magnitude than Unlike did have upon alone, when AAP + cisplatin. Both had markedly increased injury AAP + cisplatin relative either drug alone. The toxic effects partially reversed concurrent administration NAC. Conclusions Our results suggest that could be used as chemo-enhancement agent potentiate chemotherapeutic particularly clinical settings. Pediatr Blood Cancer 2014;61:120–127. © 2013 Wiley Periodicals, Inc.