Abstract
N-acetylcysteine (NAC), often used as an antioxidant-scavenging reactive oxygen species (ROS) in vitro, was recently shown to increase the cytotoxicity of other compounds through ROS-dependent and ROS-independent mechanisms. In this study, NAC itself was found to induce extensive ROS production in human leukemia HL-60 and U937 cells. The cytotoxicity depends on ROS-modulating enzyme expression. In HL-60 cells, NAC activated NOX2 to produce superoxide (O2•−). Its subsequent conversion into H2O2 by superoxide dismutase 1 and 3 (SOD1, SOD3) and production of ClO− from H2O2 by myeloperoxidase (MPO) was necessary for cell death induction. While the addition of extracellular SOD potentiated NAC-induced cell death, extracellular catalase (CAT) prevented cell death in HL-60 cells. The MPO inhibitor partially reduced the number of dying HL-60 cells. In U937 cells, the weak cytotoxicity of NAC is probably caused by lower expression of NOX2, SOD1, SOD3, and by the absence of MOP expression. However, even here, the addition of extracellular SOD induced cell death in U937 cells, and this effect could be reversed by extracellular CAT. NAC-induced cell death exhibited predominantly apoptotic features in both cell lines. Conclusions: NAC itself can induce extensive production of O2•− in HL-60 and U937 cell lines. The fate of the cells then depends on the expression of enzymes that control the formation and conversion of ROS: NOX, SOD, and MPO. The mode of cell death in response to NAC treatment bears apoptotic and apoptotic-like features in both cell lines.
Highlights
N-acetylcysteine (NAC), despite its low bioavailability, has long been used in medicine for a wide range of conditions
We observed that NAC, depending on concentration used, induced extensive loss of viability in HL-60 cells (Figure 1a)
U937 cells were only marginally affected by the same treatment (Figure 1b)
Summary
N-acetylcysteine (NAC), despite its low bioavailability, has long been used in medicine for a wide range of conditions. It is a mucolytic agent in patients with a variety of respiratory illnesses, including cystic fibrosis. NAC exhibits beneficial immune-modulation activity in patients with HIV. A detailed overview of NAC clinical applications can be found in the literature [1,2,3,4]. Its mechanism of action in clinics is mainly attributed to (a) its ability to reduce disulfide bonds and (b) to serve as a precursor of glutathione (GSH) synthesis [2,4,5]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.