丙酮酸乙酯可对抗人类白血病细胞，但对正常血细胞无害。
Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells.
作者信息
Birkenmeier Gerd, Hemdan Nasr Y A, Kurz Susanne, Bigl Marina, Pieroh Philipp, Debebe Tewodros, Buchold Martin, Thieme Rene, Wichmann Gunnar, Dehghani Faramarz
机构信息
Institute of Biochemistry, Medical Faculty, University of Leipzig, Johannisallee 30, 04103 Leipzig, Germany.
Department of Orthopedics, Trauma and Plastic Surgery, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany.
出版信息
PLoS One. 2016 Aug 31;11(8):e0161571. doi: 10.1371/journal.pone.0161571. eCollection 2016.
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.
丙酮酸乙酯是一种已知的活性氧清除剂和抗炎药物，被发现可对抗白血病细胞。通过坏死/凋亡诱导、ATP耗竭以及抑制糖酵解和副糖酵解酶的协同作用实现肿瘤细胞杀伤。乳酸乙酯对白血病细胞的危害较小，但被发现可使细胞周期停滞在G0/G1期。丙酮酸乙酯和乳酸乙酯均被鉴定为糖原合成酶激酶-3β（GSK-3β）的新型抑制剂。尽管丙酮酸乙酯对白血病细胞有强烈作用，但人类同源血细胞仅受到轻微影响。数据通过免疫印迹、流式细胞术、酶活性测定和基因阵列分析进行汇总。我们的结果揭示了丙酮酸乙酯诱导细胞死亡的新机制，从而为白血病肿瘤提供了一种具有高治疗窗的新治疗方案。
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