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Sulfiredoxin inhibitor induces preferential death of cancer cells through reactive oxygen species-mediated mitochondrial damage

Title
Sulfiredoxin inhibitor induces preferential death of cancer cells through reactive oxygen species-mediated mitochondrial damage
Authors
Kim, HojinLee, Gong-RakKim, JiwonBaek, Jin YoungJo, You JinHong, Seong-EunKim, Sung HoonLee, JiaeLee, Hye InPark, Song-KyuKim, Hwan MookLee, Hwa JeongChang, Tong-ShinRhee, Sue GooLee, Ju-SeogJeong, Woojin
Ewha Authors
이화정정우진창동신
SCOPUS Author ID
이화정scopus; 정우진scopus; 창동신scopus
Issue Date
2016
Journal Title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN
0891-5849JCR Link1873-4596JCR Link
Citation
vol. 91, pp. 264 - 274
Keywords
SulfiredoxinCancerReactive oxygen speciesApoptosisMitochondrial damage
Publisher
ELSEVIER SCIENCE INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Recent studies have shown that many types of cancer cells have increased levels of reactive oxygen species (ROS) and enhance antioxidant capacity as an adaptation to intrinsic oxidative stress, suggesting that cancer cells are more vulnerable to oxidative insults and are more dependent on antioxidant systems compared with normal cells. Thus, disruption of redox homeostasis caused by a decline in antioxidant capacity may provide a method for the selective death of cancer cells. Here we show that ROS-mediated selective death of tumor cells can be caused by inhibiting sulfiredoxin (Srx), which reduces hyperoxidized peroxiredoxins, leading to their reactivation. Srx inhibitor increased the accumulation of sulfuric peroxiredoxins and ROS, which led to oxidative mitochondrial damage and caspase activation, resulting in the death of A549 human lung adenocarcinoma cells. Srx depletion also inhibited the growth of A549 cells like Srx inhibition, and the cytotoxic effects of Srx inhibitor were considerably reversed by Srx overexpression or antioxidants such as N-acetyl cysteine and butylated hydroxyanisol. Moreover, Srx inhibitor rendered tumorigenic ovarian cells more susceptible to ROS-mediated death compared with nontumorigenic cells and significantly suppressed the growth of A549 xenografts without acute toxicity. Our results suggest that Srx might serve as a novel therapeutic target for cancer treatment based on ROSmediated cell death. (C) 2015 Elsevier Inc. All rights reserved.
DOI
10.1016/j.freeradbiomed.2015.12.023
Appears in Collections:
약학대학 > 약학과 > Journal papers
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