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Experimental and Molecular Therapeutics

Resistance to alkylating anticancer drugs: Role of the Nrf2-antioxidant system

Sarala Manandhar, Jeong-Min Cho, Hyun-Min Park and Mi-Kyoung Kwak
Sarala Manandhar
Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do, Republic of Korea
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Jeong-Min Cho
Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do, Republic of Korea
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Hyun-Min Park
Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do, Republic of Korea
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Mi-Kyoung Kwak
Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do, Republic of Korea
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DOI:  Published May 2008
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AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

Abstract

705

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.

Footnotes

  • 99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

  • American Association for Cancer Research
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Cancer Research: 68 (9 Supplement)
May 2008
Volume 68, Issue 9 Supplement
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Resistance to alkylating anticancer drugs: Role of the Nrf2-antioxidant system
Sarala Manandhar, Jeong-Min Cho, Hyun-Min Park and Mi-Kyoung Kwak
Cancer Res May 1 2008 (68) (9 Supplement) 705;

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Resistance to alkylating anticancer drugs: Role of the Nrf2-antioxidant system
Sarala Manandhar, Jeong-Min Cho, Hyun-Min Park and Mi-Kyoung Kwak
Cancer Res May 1 2008 (68) (9 Supplement) 705;
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Cancer Research Online ISSN: 1538-7445
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