Glucose-dependent active ATP depletion by koningic acid kills high-glycolytic cells
Glucose-dependent active ATP depletion by koningic acid kills high-glycolytic cells
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DOI：
10.1016/j.bbrc.2007.10.199
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发表时间：
2008-01-11
影响因子：
3.1
通讯作者：
Hasumi, Keiji
中科院分区：
文献类型：
--
作者：
Kumagai, Shohei;Narasaki, Ritsuko;Hasumi, Keiji
即使在有氧条件下，许多类型的癌细胞也严重依赖糖酵解来产生能量。我们发现koningic acid （KA）是一种甘油醛-3-磷酸脱氢酶（GAPDH）抑制剂，通过葡萄糖依赖性活性ATP剥夺选择性杀死高糖酵解细胞。在7个肿瘤细胞系中，6个具有高糖酵解能力的细胞系的生长受到KA的抑制，而3个具有低糖酵解能力的正常细胞系对KA不敏感。敏感细胞的生长抑制和不依赖caspase的细胞死亡与葡萄糖磷酸化促进的严重ATP消耗有关。虽然GAPDH在ka不敏感的CHO-KI细胞中被完全抑制，但ka介导的ATP消耗不那么广泛和短暂，可能是由于利用生酮必需氨基酸作为能量来源。KA在体内抑制了埃利希腹水肿瘤的生长，有利于小鼠的生存。(c) 2007爱思唯尔公司版权所有。
Many types of cancer cells depend heavily on glycolysis for energy production even in aerobic conditions. We found that koningic acid (KA), an inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), selectively kills high-glycolytic cells through glucose-dependent active ATP deprivation. Out of seven tumor cell lines tested, growth of six cell lines, which had high glycolytic capacity, was inhibited by KA, whereas three normal cell lines, which had low glycolytic activity, were insensitive to KA. The growth inhibition and caspase-independent cell death in sensitive cells were related to severe ATP depletion that was promoted by glucose phosphorylation. Although GAPDH was completely inhibited in KA-insensitive CHO-KI cells, KA-mediated ATP depletion was less extensive and transient, possibly due to utilization of ketogenic essential amino acids as energy source. KA suppressed Ehrlich ascites tumor growth in vivo and benefited the survival of the affected mice. (c) 2007 Elsevier Inc. All rights reserved.