Flavonoid-induced glutathione depletion: Potential implications for cancer treatment
Flavonoid-induced glutathione depletion: Potential implications for cancer treatment
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DOI：
10.1016/j.freeradbiomed.2006.03.002
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发表时间：
2006-07-01
影响因子：
7.4
通讯作者：
Day, Brian J.
中科院分区：
文献类型：
--
作者：
Kachadourian, Remy;Day, Brian J.
在人肺(A549)、髓系(HL-60)和前列腺癌(PC-3)肿瘤细胞中检测了几种黄酮类化合物诱导谷胱甘肽(GSH)耗竭的能力。在A549和HL-60细胞中，羟基查尔酮(2‘-HC)和双羟查尔酮(2’，2-，2‘，3-，2，4-和2’，5-DHC)的作用效果最好，在25 mM照射4h内消耗50%以上的细胞内GSH；而在PC-3细胞中，黄酮类化合物白杨素和芹菜素作用最有效，在25mM作用24 h内消耗50%-70%的细胞内GSH。随后测试了原型黄酮类化合物(2‘，5-DHC和白杨素)增强促氧化剂(依托泊苷、鱼藤酮、2-甲氧基雌二醇和姜黄素)的毒性的能力。在A549细胞中，2‘，5’-DHC可增强鱼藤酮、2-甲氧基雌二醇和姜黄素的细胞毒作用，但不能增强依托泊苷的细胞毒作用。在HL-60和PC-3细胞中，白杨素增强了姜黄素的细胞毒性，而催化抗氧化剂锰(III)meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin(MnTE-2-PYP)可减弱其细胞毒性。对线粒体GSH水平、线粒体膜电位和细胞色素c释放的评估表明，2，5‘-DHC和白杨素诱导的增强作用涉及线粒体功能障碍。(C)2006 Elsevier Inc.保留所有权利。
The ability of a number of flavonoids to induce glutathione (GSH) depletion was measured in lung (A549), myeloid (HL-60), and prostate (PC-3) human tumor cells. The hydroxychalcone (2'-HC) and the dilrydroxychalcones (2',2-, 2',3-, 2,4-, and 2',5-DHC) were the most effective in A549 and HL-60 cells, depleting more than 50% of intracellular GSH within 4 h of exposure at 25 mu M. In contrast, the flavones chrysin and apigenin were the most effective in PC-3 cells, depleting 50-70% of intracellular GSH within 24 h of exposure at 25 mu M. In general, these flavonoids were more effective than three classical substrates of multidrug resistance protein 1 (MK-571, indomethacin, and verapamil). Prototypic flavonoids (2',5-DHC and chrysin) were subsequently tested for their abilities to potentiate the toxicities of prooxidants (etoposide, rotenone, 2-methoxyestradiol, and curcumin). In A549 cells, 2',5'-DHC potentiated the cytotoxicities of rotenone, 2-methoxyestradiol, and curcumin, but not etoposide. In HL-60 and PC-3 cells, chrysin potentiated the cytotoxicity of curcumin, cytotoxicity that was attenuated by the catalytic antioxidant manganese(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP). Assessments of mitochondrial GSH levels mitochondrial membrane potential and cytochrome c release showed that the potentiation effects induced by 2,5'-DHC and chrysin involve mitochondrial dysfunction. (c) 2006 Elsevier Inc. All rights reserved.