Glycolaldehyde induces growth inhibition and oxidative stress in human breast cancer cells
Glycolaldehyde induces growth inhibition and oxidative stress in human breast cancer cells
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DOI：
10.1016/j.freeradbiomed.2005.10.065
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发表时间：
2006-04-01
影响因子：
7.4
通讯作者：
Benov, LT
中科院分区：
文献类型：
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作者：
Al-Enezi, KS;Alkhalaf, M;Benov, LT
乙醇醛 (GA) 是由葡萄糖的氧化降解、糖化蛋白、脂质过氧化和氨基酸氧化以及人类中性粒细胞在吞噬过程中形成的。吞噬细胞产生 GA 的确切目的尚不清楚，但很容易推测它是防御入侵细菌和肿瘤细胞的一部分。我们已经报道了 GA 诱导乳腺癌细胞凋亡。由于GA羰基不能通过环化作用被封闭，因此很容易发生烯醇化，随后被空气氧化，同时生成乙二醛和超氧化物。由于这两种产品都会诱发氧化应激，因此在这项工作中我们重点研究 GA 引起氧化细胞损伤的能力。 MCF7 人乳腺癌细胞与不同 GA 浓度一起孵育，并评估 O-2（中心点-）的产生、脂质过氧化和羰基化蛋白质。 20 μM 的 GA 具有细胞毒性，抑制细胞增殖，100 μM 的 GA 诱导 p53 表达并引起细胞凋亡。这些事件伴随着 O-2（中心点）产生的增加、脂质过氧化和蛋白质羰基的积累。因此，α-羟基醛似乎可以诱导氧化应激。然而，预防氧化应激并不能消除 GA 对细胞生长和活力的影响，这似乎是乙二醛毒性的直接后果。 (c) 2005 Elsevier Inc. 保留所有权利。
Glycolaldehyde (GA) is formed by oxidative degradation of glucose, from glycated proteins, lipid peroxidation, and oxidation of amino acids, and by human neutrophils during phagocytosis. The exact purpose of GA production by phagocytes is unclear, but it is tempting to speculate that it is part of the defense against invading bacteria and tumor cells. We have already reported that GA induces apoptosis in breast cancer cells. Because the GA carbonyl group cannot be blocked by cyclization, it is prone to enolization followed by air oxidation with concomitant production of glyoxal and superoxide. Since both these products can induce oxidative stress, in this work we focused on the ability of GA to cause oxidative cell damage. MCF7 human breast cancer cells were incubated with different GA concentrations and O-2(center dot-) production, lipid peroxidation, and carbonylated protein were assessed. GA was cytotoxic at 20 mu M, inhibiting cell proliferation, and at 100 mu M, induced p53 expression and caused apoptosis. These events were accompanied by increases of O-2(center dot-) production, lipid peroxidation, and accumulation of protein carbonyl. It thus appears that a-hydroxy aldehydes can induce oxidative stress. Prevention of oxidative stress, however, did not abolish the effects of GA on cell growth and viability, which appeared to be a direct consequence of glyoxal toxicity. (c) 2005 Elsevier Inc. All rights reserved.