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Drug resistance to 5-FU linked to reactive oxygen species modulator 1

Authors
 In Tae Hwang  ;  Young Min Chung  ;  Young Do Yoo  ;  Jun Suk Kim  ;  Hyung Jung Kim  ;  Byung Soo Kim  ;  Jin Sil Chung  ;  Jung Jin Kim 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.359(2) : 304-310, 2007 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2007
Abstract
While acute oxidative stress triggers cell apoptosis or necrosis, persistent oxidative stress induces genomic instability and has been implicated in tumor progression and drug resistance. In a previous report, we demonstrated that reactive oxygen species modulator 1 (Romo1) expression was up-regulated in most cancer cell lines and suggested that increased Romo1 expression might confer chronic oxidative stress to tumor cells. In this study, we show that enforced Romo1 expression induces reactive oxygen species (ROS) production in the mitochondria leading to massive cell death. However, tumor cells that adapt to oxidative stress by increasing manganese superoxide dismutase (MnSOD), Prx I, and Bcl-2 showed drug resistance to 5-FU. To elucidate the relationship between 5-FU-induced ROS production and Romo1 expression, Romo1 siRNA was used to inhibit 5-FU-triggered Romo1 induction. Romo1 siRNA treatment efficiently blocked 5-FU-induced ROS generation, demonstrating that 5-FU treatment stimulated ROS production through Romo1 induction. Based on these results we suggest that cellular adaptive response to Romo1-induced ROS is another mechanism of drug resistance to 5-FU and Romo1 expression may provide a new clinical implication in drug resistance of cancer chemotherapy.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X07010492
DOI
10.1016/j.bbrc.2007.05.088
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyung Jung(김형중) ORCID logo https://orcid.org/0000-0003-2498-0683
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95694
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