Abstract
The treatment of alkylating cytotoxic drug cisplatin is often limited by high incidence rate of resistance. In the present study, the potential involvement of the transcription factor Nrf2 in determination of cisplatin cytotoxicity has been investigated. Nrf2-deficient murine embryonic fibroblasts showed increased cell death, cytotoxicity, and apoptosis in response to cisplatin treatment compared to wild-type cells. Cisplatin-resistant human ovarian cancer SK-OV cells, which are retaining 25-fold higher levels of GSH than murine fibroblasts, could be sensitized by inhibition of Nrf2. Transfection with Nrf2 siRNA into SK-OV cells resulted in severe degree of GSH depletion and exacerbated cytotoxicity following cisplatin treatment compared to scrambled RNA control. In conclusion, we propose that the Nrf2 pathway, which plays a protective role in normal cells, can be a potential target to control cancer cell resistance to oxidants, cytotoxic chemicals, and radiation.
| Original language | English |
|---|---|
| Pages (from-to) | 96-108 |
| Number of pages | 13 |
| Journal | Cancer Letters |
| Volume | 260 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - 18 Feb 2008 |
Bibliographical note
Funding Information:We thank Dr. Nobunao Wakabayashi for providing murine embryonic fibroblasts from wild-type and nrf2 -deficient mice. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST, R01-2007-000-10890-0).
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Keywords
- Cisplatin
- GSH
- Nrf2
- Ovarian cancer cells
- Resistance
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