Reactive oxygen species and PI3K/Akt signaling play key roles in the induction of Nrf2-driven heme oxygenase-1 expression in sulforaphane-treated human mesothelioma MSTO-211H cells

被引:108
作者
Lee, Yoon-Jin [1 ,2 ]
Jeong, Hyang-Yun [3 ]
Kim, Yong-Bae [2 ]
Lee, Yong-Jin [2 ]
Won, Seong Youn [4 ]
Shim, Jung-Hyun [1 ]
Cho, Moon-Kyun [4 ]
Nam, Hae-Seon [4 ]
Lee, Sang-Han [1 ,2 ]
机构
[1] Soonchunhyang Univ, Dept Biochem, Coll Med, Cheonan 330090, South Korea
[2] Soonchunhyang Univ, Cheonan Hosp, Coll Med, Soonchunhyung Environm Hlth Ctr Asbestos Related, Cheonan 330090, South Korea
[3] Chungbuk Sci High Sch, Cheongwon 363853, Chungbuk, South Korea
[4] Soonchunhyang Univ, Soonchunhyang Med Res Inst, Div Mol Canc Res, Cheonan 330090, South Korea
关键词
Sulforaphane; Reactive oxygen species; Nrf2; PI3K/Akt; Heme oxygenase-1; OVARIAN-CANCER CELLS; PROSTATE-CANCER; MOLECULAR-MECHANISMS; CYCLE ARREST; HEPG2; CELLS; IN-VITRO; NRF2; APOPTOSIS; PATHWAYS; ENZYMES;
D O I
10.1016/j.fct.2011.10.035
中图分类号
TS2 [食品工业];
学科分类号
100403 [营养与食品卫生学];
摘要
The nuclear factor erythroid-derived 2 related factor 2 (Nrf2)/heme oxygenase (HO)-1 induction plays cytoprotective roles against oxidative injury, apoptosis, and anticancer therapy; however, little is known about its regulation in human mesothelioma MSTO-211H cells. In this study, we investigated Nrf2/HO-1 induction in response to sulforaphane and determined the signaling pathways involved in this process. Sulforaphane treatment decreased cell viability and triggered a rapid and transient increase in the intracellular ROS levels. Pretreatment with N-acetylcysteine (NAC) prevented sulforaphane-induced cytotoxicity. Erk1/2 was activated within 1 h of sulforaphane addition, whereas Akt phosphorylation was suppressed until the first 8 h, and was then maintained at an elevated level until 72 h, displaying a biphasic regulatory feature. Nrf2 protein levels in both nuclear and whole cell lysates were increased after sulforaphane treatment and were decreased by pretreatment with NAC, actinomycin D and cycloheximide. Activation of the Nrf2/HO-1 system after sulforaphane treatment was suppressed by pretreatment with NAC or Ly294002, a PI3K inhibitor. Knockdown of Nrf2 with siRNA decreased cell viability and attenuated sulforaphane-induced HO-1 up-regulation. Overall, our results indicate that ROS generation and/or activation of PI3K/Akt signaling regulate cell survival and Nrf2-driven HO-1 expression in sulforaphane-treated MSTO-211H cells. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:116 / 123
页数:8
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