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

Guangshan Zhao; Ruixia Dong; Jianyuan Teng; Lian Yang; Tao Liu; Ximing Wu; Yufeng He; Zhiping Wang; Hanlin Pu; Yifei Wang

doi:10.1021/acsomega.0c01034

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

ACS Omega. 2020 May 12;5(20):11710-11720. doi: 10.1021/acsomega.0c01034. eCollection 2020 May 26.

Authors

Guangshan Zhao¹, Ruixia Dong², Jianyuan Teng¹, Lian Yang³, Tao Liu¹, Ximing Wu⁴, Yufeng He⁴, Zhiping Wang³, Hanlin Pu¹, Yifei Wang¹

Affiliations

¹ Biology Postdoctoral Research Station, Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, P. R. China.
² Department of Forestry and Technology, Lishui Vocational and Technical College, Lishui, Zhejiang 323000, P. R. China.
³ Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P. R. China.
⁴ Laboratory of Redox Biology, State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui 230036, P. R. China.

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.