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songxinxing

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http://www.spandidos-publications.com/ijo/40/2/501
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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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; W% q0 D6 j3 c& q0 R! NAuthors: Heinrich Sauer, Steffi Engel, Nada Milosevic, Fatemeh Sharifpanah, Maria Wartenberg 8 k8 |% W/ T9 H: o/ y
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Affiliations: Department of Physiology, Justus Liebig University Giessen, Aulweg 129, D-35392 Giessen, Germany
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Published online on: Thursday, October 13, 2011 4 g6 F0 }; J# `+ U/ m
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Doi: 10.3892/ijo.2011.1230 3 h2 l9 z0 O  y* y  Y3 ?+ V1 V

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/ G; W1 i/ y! |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 2 u9 j4 x) `1 [5 F! f
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