title: Resveratrol has anti-leukemic activity associated with decreased O-GlcNAcylated proteins.
abstract: CLL cells are characterized by high levels of proteins that are post-translationally modified by O-linked β-N-acetylglucosamine (O-GlcNAc) moieties, but it is not clear whether O-GlcNAc is a relevant therapeutic target. The neutraceutical resveratrol is cytotoxic to chronic lymphocytic leukemia cells in vitro. In this study, we found that resveratrol has therapeutic activity as a single agent in vivo in both human chronic lymphocytic leukemia patients and mice with erythroleukemia. Blood and splenic O-GlcNAc levels reflected the changes in tumor burden. Resveratrol directly lowered O-GlcNAc levels in leukemia cells through proteasomal activation, but increasing O-GlcNAc levels in vitro did not prevent cell death. These findings suggest that resveratrol has potential as a novel treatment for some forms of chronic and acute leukemia, and the measurement of O-GlcNAc levels could be a surrogate marker for therapeutic responses.
authors.affiliation: Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Jelena
authors.initials: J
authors.lastname: Tomic
authors.forename: Lindsay
authors.initials: L
authors.lastname: McCaw
authors.forename: Youjun
authors.initials: Y
authors.lastname: Li
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Hough
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Ben-David
authors.forename: Jason
authors.initials: J
authors.lastname: Moffat
authors.forename: David E
authors.initials: DE
authors.lastname: Spaner
mesh_terms: D016475:3T3 Cells; D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D004336:Drug Antagonism; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D011506:Proteins; D013267:Stilbenes; D007372:Interferons; D000077185:Resveratrol; D000117:Acetylglucosamine