title: Evaluation of resveratrol and N-acetylcysteine for cancer chemoprevention in a Fanconi anemia murine model.
abstract: Fanconi anemia (FA) patients suffer from progressive bone marrow failure and often develop cancers. Previous studies showed that antioxidants tempol and resveratrol (RV) delayed tumor onset and reduced hematologic defects in FA murine models, respectively. Here we tested whether antioxidants N-acetylcysteine (NAC) or RV could delay cancer in tumor prone Fancd2(-/-) /Trp53(+/-) mice. Unlike tempol, neither compound had any significant chemopreventive effect in this model. We conclude that not all anti-oxidants are chemopreventive in FA. In addition, when given to Fancd2(-/-) mice, NAC helped maintain Fancd2(-/-) KSL cells in quiescence while tempol did not. The mechanisms behind the different actions of these antioxidants await further investigation.
authors.affiliation: Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon.
authors.forename: Qing-Shuo
authors.initials: QS
authors.lastname: Zhang
authors.forename: Laura
authors.initials: L
authors.lastname: Marquez-Loza
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Sheehan
authors.forename: Kevin
authors.initials: K
authors.lastname: Watanabe-Smith
authors.forename: Laura
authors.initials: L
authors.lastname: Eaton
authors.forename: Eric
authors.initials: E
authors.lastname: Benedetti
authors.forename: Angela
authors.initials: A
authors.lastname: Major
authors.forename: Kathryn
authors.initials: K
authors.lastname: Schubert
authors.forename: Matthew
authors.initials: M
authors.lastname: Deater
authors.forename: Eric
authors.initials: E
authors.lastname: Joseph
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D005199:Fanconi Anemia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000502:physiology*; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D000975:Antioxidants; C499904:Fancd2 protein, mouse; D052236:Fanconi Anemia Complementation Group D2 Protein; D016166:Free Radical Scavengers; D013267:Stilbenes; D016159:Tumor Suppressor Protein p53; D000077185:Resveratrol; D000111:Acetylcysteine
keywords: Fanconi anemia; N-acetylcysteine; antioxidants; chemoprevention; resveratrol