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

In Tae Hwang, Young Min Chung, Jung Jin Kim, Jin Sil Chung, Byung Soo Kim, Hyung Jung Kim, Jun Suk Kim, Young Do Yoo

Research output: Contribution to journalArticle

73 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)304-310
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number2
DOIs
Publication statusPublished - 2007 Jul 27

Fingerprint

Drug Resistance
Fluorouracil
Modulators
Reactive Oxygen Species
Pharmaceutical Preparations
Oxidative stress
Oxidative Stress
Tumors
Cells
Neoplasms
Small Interfering RNA
Mitochondria
Chemotherapy
Genomic Instability
Cell death
Superoxide Dismutase
Cell Death
Necrosis

Keywords

  • 5-FU
  • Cancer
  • Drug resistance
  • Reactive oxygen species
  • Romo1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Drug resistance to 5-FU linked to reactive oxygen species modulator 1. / Hwang, In Tae; Chung, Young Min; Kim, Jung Jin; Chung, Jin Sil; Kim, Byung Soo; Kim, Hyung Jung; Kim, Jun Suk; Yoo, Young Do.

In: Biochemical and Biophysical Research Communications, Vol. 359, No. 2, 27.07.2007, p. 304-310.

Research output: Contribution to journalArticle

Hwang, In Tae ; Chung, Young Min ; Kim, Jung Jin ; Chung, Jin Sil ; Kim, Byung Soo ; Kim, Hyung Jung ; Kim, Jun Suk ; Yoo, Young Do. / Drug resistance to 5-FU linked to reactive oxygen species modulator 1. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 359, No. 2. pp. 304-310.
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