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" e+ S, e( b. C8 W- Uhttp://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 # a/ ~' P9 m5 [4 D. z
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Authors: Heinrich Sauer, Steffi Engel, Nada Milosevic, Fatemeh Sharifpanah, Maria Wartenberg / Z/ M/ p- P; p# p7 f: V: B

  ^3 u; U0 J3 r9 t4 dAffiliations: Department of Physiology, Justus Liebig University Giessen, Aulweg 129, D-35392 Giessen, Germany
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8 Z- i# ~1 R( Q4 q" hPublished online on: Thursday, October 13, 2011
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( t" H1 @. {8 T  z- X: R5 U2 PDoi: 10.3892/ijo.2011.1230
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* W& G* V  D' K& U4 x( KPages: 501-508
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' I7 ^6 A5 D, r& }/ E! \# NAbstract: 1 i" m1 q$ X4 B4 S2 @4 Q0 x0 f1 X" @
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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