title: Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells.
abstract: Ethyl pyruvate, a known ROS scavenger and anti-inflammatory drug was found to combat leukemia cells. Tumor cell killing was achieved by concerted action of necrosis/apoptosis induction, ATP depletion, and inhibition of glycolytic and para-glycolytic enzymes. Ethyl lactate was less harmful to leukemia cells but was found to arrest cell cycle in the G0/G1 phase. Both, ethyl pyruvate and ethyl lactate were identified as new inhibitors of GSK-3β. Despite the strong effect of ethyl pyruvate on leukemia cells, human cognate blood cells were only marginally affected. The data were compiled by immune blotting, flow cytometry, enzyme activity assay and gene array analysis. Our results inform new mechanisms of ethyl pyruvate-induced cell death, offering thereby a new treatment regime with a high therapeutic window for leukemic tumors.
authors: Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
authors: Gerd
authors: G
authors: Birkenmeier
authors: Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
authors: Nasr Y A
authors: NY
authors: Hemdan
authors: Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
authors: Susanne
authors: S
authors: Kurz
authors: Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
authors: Marina
authors: M
authors: Bigl
authors: Department of Orthopedics, Trauma and Plastic Surgery, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany.|Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06097 Halle (Saale), Germany.
authors: Philipp
authors: P
authors: Pieroh
authors: Institute of Medical Microbiology, Medical Faculty, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany.|College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
authors: Tewodros
authors: T
authors: Debebe
authors: Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
authors: Martin
authors: M
authors: Buchold
authors: University Medical Center, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University of Leipzig, Liebigstr. 19, 04103 Leipzig, Germany.
authors: Rene
authors: R
authors: Thieme
authors: ENT-Research Lab, Department of Otolaryngology, Head and Neck Surgery, University Hospital Leipzig, Medical Faculty, University of Leipzig, Liebigstr. 21, 04103 Leipzig, Germany.
authors: Gunnar
authors: G
authors: Wichmann
authors: Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06097 Halle (Saale), Germany.
authors: Faramarz
authors: F
authors: Dehghani
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D009363:Neoplasm Proteins; D011773:Pyruvates; C046522:ethyl pyruvate; D000255:Adenosine Triphosphate; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta