Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: Implication to cancer cell resistance

被引：141

作者：

Cho, Jeong-Min ^{[1
]}

Manandhar, Sarala ^{[1
]}

Lee, Hyang-Rim ^{[1
]}

Park, Hyun-Min ^{[1
]}

Kwak, Mi-Kyoung ^{[1
]}

机构：

[1] Yeungnam Univ, Coll Pharm, Gyongsan 712749, Gyeongsangbuk D, South Korea

来源：

CANCER LETTERS | 2008年 / 260卷 / 1-2期

关键词：

Nrf2; cisplatin; GSH; ovarian cancer cells; resistance;

D O I：

10.1016/j.canlet.2007.10.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

引用

页码：96 / 108

页数：13

共 49 条

[41] Increased expression of nuclear factor E2 P45-related factor 2 (NRF2) in head and neck squamous cell carcinomas
Stacy, Donnie R.
Ely, Kim
Massion, Pierre P.
Yarbrough, Wendell G.
Hallahan, Dennis E.
Sekhar, Konjeti R.
Freeman, Michael L.
[J]. HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2006, 28 (09): : 813 - 818
[42] Surh YJ, 2005, J NUTR, V135, p2993S, DOI 10.1093/jn/135.12.2993S
[43] Thimmulappa RK, 2002, CANCER RES, V62, P5196
[44] Thomas Hilary, 2003, Cancer Control, V10, P159
[45] Effect of glutathione depletion on antitumor drug toxicity (apoptosis and necrosis) in U-937 human promonocytic cells -: The role of intracellular oxidation
Troyano, A
Fernández, C
Sancho, P
de Blas, E
Aller, P
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (50) : 47107 - 47115
[46] Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation
Wakabayashi, N
Itoh, K
Wakabayashi, J
Motohashi, H
Noda, S
Takahashi, S
Imakado, S
Kotsuji, T
Otsuka, F
Roop, DR
Harada, T
Engel, JD
Yamamoto, M
[J]. NATURE GENETICS, 2003, 35 (03) : 238 - 245
[47] Cellular processing of platinum anticancer drugs
Wang, D
Lippard, SJ
[J]. NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (04) : 307 - 320
[48] Generation of a stable antioxidant response element-driven reporter gene cell line and its use to show redox-dependent activation of Nrf2 by cancer chemotherapeutic agents
Wang, Xiu Jun
Hayes, John D.
Wolf, C. Roland
[J]. CANCER RESEARCH, 2006, 66 (22) : 10983 - 10994
[49] YAO KS, 1995, CANCER RES, V55, P4367

← 1 2 3 4 5 →