N-Acetylcysteine interacts with copper to generate hydrogen peroxide and selectively induce cancer cell death.

Abstract

A variety of metal-binding compounds have been found to exert anti-cancer activity. We postulated that N-acetylcysteine (NAC), which is a membrane-permeable metal-binding compound, might have anti-cancer activity in the presence of metals. We found that NAC/Cu(II) significantly alters growth and induces apoptosis in human cancer lines, yet NAC/Zn(II) and NAC/Fe(III) do not. We further confirmed that this cytotoxicity of NAC/Cu(II) is attributed to reactive oxygen species (ROS). These findings indicate that the combination of Cu(II) and thiols generates cytotoxic ROS that induce apoptosis in cancer cells. They also indicate a fourth class of anti-neoplastic metal-binding compounds, the "ROS generators".

• Authors: Jie Zheng, Jessica R Lou, Xiao-Xi Zhang, Doris M Benbrook, Marie H Hanigan, Stuart E Lind, Wei-Qun Ding
• Journal: Cancer letters (Cancer Lett) Vol. 298 Issue 2 Pg. 186-94 (Dec 08 2010) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 20667650 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Copper
• Hydrogen Peroxide
• Poly(ADP-ribose) Polymerases
• Caspase 3
• Acetylcysteine

Topics

• Acetylcysteine (chemistry, pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Caspase 3 (metabolism)
• Cell Line
• Cell Line, Tumor
• Cell Survival (drug effects)
• Copper (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Humans
• Hydrogen Peroxide (metabolism)
• Microscopy, Confocal
• Neoplasms (metabolism, pathology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Reactive Oxygen Species (metabolism)