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.
|Number of pages
|Biochemical and biophysical research communications
|Published - 2007 Jul 27
Bibliographical noteFunding Information:
This work was supported by a Grant (FG06-2-20) of the 21C Frontier Functional Human Genome Project from the Ministry of Science & Technology in Korea, by a Grant (R01-2006-000-10113-0) from the Basic Research Program of the Korea Science & Engineering Foundation, and by a Grant (R11-2005-017-01001-0) of the Research Center for Woman’s Diseases of the KOSEF.
- Drug resistance
- Reactive oxygen species
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology