NAC (N-acetyl-L-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H2O2. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis.
Skip Nav Destination
Article navigation
September 2013
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
August 09 2013
ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors
Marianna Halasi;
Marianna Halasi
*Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
Search for other works by this author on:
Ming Wang;
Ming Wang
*Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
Search for other works by this author on:
Tanmay S. Chavan;
Tanmay S. Chavan
†Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, U.S.A.
Search for other works by this author on:
Vadim Gaponenko;
Vadim Gaponenko
†Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, U.S.A.
Search for other works by this author on:
Nissim Hay;
Nissim Hay
†Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, U.S.A.
‡Research and Development Section, Jesse Brown VA Medical Center, Chicago, IL 60612, U.S.A.
Search for other works by this author on:
Andrei L. Gartel
Andrei L. Gartel
1
*Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, U.S.A.
†Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, U.S.A.
1To whom correspondence should be addressed (email agartel@uic.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
February 21 2013
Revision Received:
June 15 2013
Accepted:
June 18 2013
Accepted Manuscript online:
June 18 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 454 (2): 201–208.
Article history
Received:
February 21 2013
Revision Received:
June 15 2013
Accepted:
June 18 2013
Accepted Manuscript online:
June 18 2013
Citation
Marianna Halasi, Ming Wang, Tanmay S. Chavan, Vadim Gaponenko, Nissim Hay, Andrei L. Gartel; ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors. Biochem J 1 September 2013; 454 (2): 201–208. doi: https://doi.org/10.1042/BJ20130282
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.