N-Acetyl-l-cysteine Enhances the Effect of Selenium Nanoparticles on Cancer Cytotoxicity by Increasing the Production of Selenium-Induced Reactive Oxygen Species.

Abstract

Peritoneal carcinomatosis (PC) has an extremely poor prognosis, which leads to a significantly decreased overall survival in patients with peritoneal implantation of cancer cells. Administration of sodium selenite by intraperitoneal injection is highly effective in inhibiting PC. Our previous study found that selenium nanoparticles (SeNPs) have higher redox activity and safety than sodium selenite. In the present study, we examined the therapeutic effect of SeNPs on PC and elucidated the potential mechanism. Our results revealed that intraperitoneal delivery of SeNPs to cancer cells in the peritoneal cavity of mice at a tolerable dose was beneficial for prolonging the survival time of mice, even better than the optimal dose of cisplatin. The underlying mechanism involved in SeNP-induced reactive oxygen species (ROS) production caused protein degradation and apoptotic response in cancer cells. Interestingly, N-acetyl-l-cysteine (NAC), recognized as a ROS scavenger, without reducing the efficacy of SeNPs, enhanced ROS production and cytotoxicity. The effect of NAC was associated with the following mechanisms: (1) the thiol groups in NAC can increase the biosynthesis of endogenous glutathione (GSH), thus increasing the production of SeNP-induced ROS and cytotoxicity and (2) redox cycling of SeNPs was directly driven by thiol groups in NAC to produce ROS. Moreover, NAC, without increasing the systematic toxicity of SeNPs, decreased SeNP-induced lethality in healthy mice. Overall, we demonstrated that SeNPs exert a potential cytotoxicity effect by inducing ROS production in cancer cells; NAC effectively heightens the property of SeNPs in vitro and in vivo.

• Authors: Guangshan Zhao, Ruixia Dong, Jianyuan Teng, Lian Yang, Tao Liu, Ximing Wu, Yufeng He, Zhiping Wang, Hanlin Pu, Yifei Wang
• Journal: ACS omega (ACS Omega) Vol. 5 Issue 20 Pg. 11710-11720 (May 26 2020) ISSN: 2470-1343 [Electronic] United States
• PMID: 32478262 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 American Chemical Society.