Journal article

Publication year: 2012

Pages: 501-508

Journal: International Journal of Oncology

Volume number: 40

Issue number: 2

ISSN: 1019-6439

eISSN: 1791-2423

Open access status: Bronze

DOI Link: https://doi.org/10.3892/ijo.2011.1230

Publisher: Spandidos Publications

Abstract: 
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 cancer cells by a signaling pathway involving ROS, activation of JNK and cleaved caspase-3.

Harvard Citation style: Sauer, H., Engel, S., Milosevic, N., Sharifpanah, F. and Wartenberg, M. (2012) 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, International Journal of Oncology, 40(2), pp. 501-508. https://doi.org/10.3892/ijo.2011.1230

APA Citation style: Sauer, H., Engel, S., Milosevic, N., Sharifpanah, F., & Wartenberg, M. (2012). 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. International Journal of Oncology. 40(2), 501-508. https://doi.org/10.3892/ijo.2011.1230