Increase in thiol oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to X-ray irradiation.
Increase in thiol oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to X-ray irradiation.
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DOI：
10.1016/j.freeradbiomed.2009.04.022
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发表时间：
2009-07-15
影响因子：
7.4
通讯作者：
Guan, Xiangming
中科院分区：
文献类型：
--
作者：
Zhao, Yong;Seefeldt, Teresa;Chen, Wei;Carlson, Laura;Stoebner, Adam;Hanson, Sarah;Foll, Ryan;Matthees, Duane P.;Palakurthi, Srinath;Guan, Xiangming
关键词：
还原型谷胱甘肽（GSH）的消耗已被广泛研究，其对癌症的辐射增敏作用。然而，很少有人知道通过增加谷胱甘肽二硫化物（GSSG）对癌症辐射敏感性的硫醇氧化应激的影响。在本研究中，通过2-乙酰氨基-3-[4-（2-乙酰氨基-2-羧基乙基硫烷基硫代羰基氨基）苯基硫代氨基甲酰基硫烷基]丙酸（2-AAPA）（一种不可逆谷胱甘肽还原酶（GR）抑制剂）有效地增加GSSG。我们的研究结果表明，GSSG增加显着增强了四种人类癌细胞系（A431，MCF 7，NCI-H226和OVCAR-3）对X射线照射的癌症敏感性。当细胞经2-AAPA预处理后再进行X射线照射时，X射线对A431、MCF 7、NCI-H226和OVCAR-3细胞的IC 50值分别从24.2±2.8、42.5±3.0、43.0±3.6和27.8±3.5戈伊降低到6.75 ±0.9、8.1±1.1、6.75±1.0和12.1±1.7戈伊。从X-射线加2-AAPA的组合观察到的协同效应与从X-射线加丁硫基磺酰亚胺（BSO）的组合观察到的协同效应相当，丁硫基磺酰亚胺（BSO）是已知增加癌症对辐射的敏感性的参考化合物。协同效应与细胞硫醇氧化应激的增加相关，这反映在GSSG增加5-6倍和总二硫化物增加25%。没有观察到GSH和总巯基的变化作为GR抑制的结果。
Depletion of reduced form glutathione (GSH) has been extensively studied for its effect on sensitizing cancer to radiation. However, little is known about the effect of thiol oxidative stress created through an increase in glutathione disulfide (GSSG) on cancer sensitivity to radiation. In this study, an increase in GSSG was effectively created by 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA), an irreversible glutathione reductase (GR) inhibitor. Our results demonstrate that the GSSG increase significantly enhanced cancer sensitivity to X-ray irradiation in four human cancer cell lines (A431, MCF7, NCI-H226 and OVCAR-3). When cells were pretreated with 2-AAPA followed by X-ray irradiation, the IC50 values of X-ray for A431, MCF7, NCI-H226 and OVCAR-3 cells were reduced from 24.2±2.8, 42.5±3.0, 43.0±3.6 and 27.8±3.5 Gy to 6.75 ±0.9, 8.1±1.1, 6.75±1.0, and 12.1±1.7 Gy respectively. The synergistic effects observed from the combination of X-ray plus 2-AAPA were comparable to that from the combination of X-ray plus buthionine sulfoximine (BSO), a reference compound known to increase cancer sensitivity to radiation. The synergistic effect was correlated with an increase in cell thiol oxidative stress which was reflected by a 5–6 fold increase in GSSG and 25% increase in total disulfides. No change in GSH and total thiols was observed as a result of GR inhibition.
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影响因子：
3.4
作者：
Biaglow, JE;Ayene, IS;Mieyal, JJ
通讯作者：
Mieyal, JJ
DOI：
10.1016/j.jpba.2008.08.033
发表时间：
2008-12-15
影响因子：
3.4
作者：
Chen, Wei;Zhao, Yong;Seefeldt, Teresa;Guan, Xiangming
通讯作者：
Guan, Xiangming
DOI：
10.1016/0360-3016(86)90210-5
发表时间：
1986-08-01
影响因子：
7
作者：
BUMP, EA;JACOBS, GP;BROWN, JM
通讯作者：
BROWN, JM
影响因子：
4.8
作者：
Aon, Miguel A.;Cortassa, Sonia;O'Rourke, Brian
通讯作者：
O'Rourke, Brian
影响因子：
3
作者：
Balcer-Kubiczek, Elizabeth K.;Attarpour, Mona;Edelman, Martin J.
通讯作者：
Edelman, Martin J.