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本帖最后由 songxinxing 于 2012-4-1 08:26 编辑 4 w! O3 f9 L8 P- a
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http://www.spandidos-publications.com/ijo/40/2/501* C# q) A5 V) Z
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Activation 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
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Authors: Heinrich Sauer, Steffi Engel, Nada Milosevic, Fatemeh Sharifpanah, Maria Wartenberg 1 J, g' s' v/ V* N7 J5 d# P2 b
5 i9 q* I* J" l0 w- cAffiliations: Department of Physiology, Justus Liebig University Giessen, Aulweg 129, D-35392 Giessen, Germany
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6 ?4 f. G/ t c2 k) v, rPublished online on: Thursday, October 13, 2011 m7 ^: Q. z4 g, r/ `
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Doi: 10.3892/ijo.2011.1230
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Pages: 501-508 9 Z [3 V( A: o0 o# h4 O
8 I7 U/ V, X( N3 dAbstract: - Z, I; ?; L$ Q8 c
The 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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