title: 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.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Lou
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Zhang
authors.forename: Doris M
authors.initials: DM
authors.lastname: Benbrook
authors.forename: Marie H
authors.initials: MH
authors.lastname: Hanigan
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Lind
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Ding
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D003300:Copper; D006861:Hydrogen Peroxide; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D000111:Acetylcysteine