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发表于 2012-4-1 08:26 |只看该作者 |倒序浏览 |打印
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本帖最后由 songxinxing 于 2012-4-1 08:26 编辑 1 ^  r# G# j! Q4 l/ s0 g% N
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http://www.spandidos-publications.com/ijo/40/2/501
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8 {3 n3 E" @- K3 U* x/ ZActivation of AMP-kinase by AICAR induces apoptosis of DU-145 prostate cancer cells through generation of reactive oxygen species and activation of c-Jun N-terminal kinase ! @. E: t* N. X& u

9 h7 p# S5 V5 G  ^1 H5 KAuthors: Heinrich Sauer, Steffi Engel, Nada Milosevic, Fatemeh Sharifpanah, Maria Wartenberg 0 I0 H- }; A+ j1 ]

8 w) {" s- [# VAffiliations: Department of Physiology, Justus Liebig University Giessen, Aulweg 129, D-35392 Giessen, Germany . d+ E9 w( X6 L" n
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Published online on: Thursday, October 13, 2011
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1 d9 D( D# P8 L/ o4 d$ _. h  j3 W6 _Doi: 10.3892/ijo.2011.1230 0 x: S: [" a  D' V) y; L( G
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Pages: 501-508
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; ~8 D8 u' p1 s0 P, z" BAbstract:
, c" S6 j! C0 L1 G# i0 hThe growth of cancer cells is limited by energy supply which is regulated by the energy sensor AMP-kinase (AMPK). Hence, mimicking a low energy state may inhibit cancer growth and may be exploited in anticancer therapies. In the present study, the impact of AMPK activation on cell growth and apoptosis of DU-145 prostate cancer cells was investigated. Incubation with the AMPK activator aminoimidazole carboxamide ribonucleotide (AICAR) dose-dependently inhibited cell growth, activated AMPK, and inhibited mTOR. Furthermore, AICAR treatment activated c-Jun N-terminal kinase (JNK) and caspase-3, thereby initiating apoptosis. Within 60 min of treatment AICAR raised intracellular reactive oxygen species (ROS) which could be abolished in the presence of the free radical scavenger N-(2-mercaptopropionyl)glycin (NMPG), the AMPK inhibitor compound C (Comp C) and the respiratory chain complex I inhibitor rotenone, but not by the NADPH oxidase inhibitor VAS2870. Inhibition of ROS generation abolished AMPK activation by AICAR as well as JNK and caspase-3 activation. Furthermore, AMPK activation, JNK phosphorylation and cleaved caspase-3 upon AICAR treatment were abolished in the presence of Comp C. In summary, our data demonstrate that activation of AMPK by AICAR induces apoptosis of prostate
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