Impact of N-acetylcysteine on antitumor activity of doxorubicin and landomycin A in NK/Ly lymphoma-bearing mice

Abstract

N-acetylcysteine (NAC) is a dietary supplement demonstrating antioxidant and liver protecting effects that is widely used in clinics. NAC is considered to possess potential therapeutic activity for health disorders characterized by generation of free oxygen radicals, as well as potential for decreasing negative side effects of various drugs. However, the mechanisms of such tissue-protective actions of NAC remain poorly understood. The main aim of this work was to study therapeutic effects of NAC applied together with the “gold standard” of chemotherapy doxorubicin (Dx) or the novel experimental drug landomycin A (LA) to mice bearing NK/Ly lymphoma. It was revealed that NAC significantly decreased the nephrotoxicity of Dx (measured as creatinine level), possessed moderate immunomodulating activity (as revealed by an increase in number of cytotoxic T-lymphocytes), and partially increased survival of NK/Ly lymphoma-bearing animals treated with Dx. On the contrary, there was little tissue-protective effect of NAC towards LA due to the weak side effects of this anticancer drug, however, the combined use of NAC and LA significantly increased survival (60+ days) of LAtreated animals with NK/Ly lymphoma. Summarizing, NAC possesses a moderate tissue-protective activity towards Dx action but lacks a major therapeutic effect. However, in the case of LA action, NAC significantly increases its anticancer activity with no impact on its negative side effects. Further studies of the molecular mechanisms underlying that activity of NAC towards the action of LA are in progress.