title: Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (review).
abstract: Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the induction of programmed cell death, largely via apoptosis but also necroptosis and autophagy. The redox-directed mechanism of action of Taurolidine is apparent from the finding that reducing agents e.g., N-acetylcysteine or glutathione impair its cytotoxicity, while its effectiveness is enhanced by agents which inhibit the cellular anti‑oxidant capacity. A similar redox-directed antineoplastic action is shown by Piperlongumine, a recently described experimental drug of plant origin. Taurolidine is particularly advantageous in surgical oncology as this taurine-derivative can be applied perioperatively or systemically with good tolerability as shown in initial clinical applications.
authors.affiliation: Institute of Pharmacology, University of Zurich and Department of Chemistry and Applied Biosciences, ETH Zurich, 8057 Zurich, Switzerland.
authors.forename: Hanns
authors.initials: H
authors.lastname: Möhler
authors.affiliation: Geistlich Pharma AG, 6110 Wolhusen, Switzerland.
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Pfirrmann
authors.affiliation: Department of Neurosurgery, University Hospital Zurich, 8091 Zurich, Switzerland.
authors.forename: Karl
authors.initials: K
authors.lastname: Frei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D002470:Cell Survival; D004148:Dioxolanes / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010084:Oxidation-Reduction / Q000187:drug effects*; D019990:Perioperative Care; D017382:Reactive Oxygen Species / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013829:Thiadiazines / Q000627:therapeutic use*; D010881:Piperidones
chemical_list: D000970:Antineoplastic Agents; D004148:Dioxolanes; D017382:Reactive Oxygen Species; D013654:Taurine; D013829:Thiadiazines; C012566:taurolidine; C498077:piperlongumine; D010881:Piperidones