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

  • Authors:
    • Heinrich Sauer
    • Steffi Engel
    • Nada Milosevic
    • Fatemeh Sharifpanah
    • Maria Wartenberg
  • View Affiliations

  • Published online on: October 13, 2011     https://doi.org/10.3892/ijo.2011.1230
  • Pages: 501-508
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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.

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February 2012
Volume 40 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
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, 501-508. https://doi.org/10.3892/ijo.2011.1230
MLA
Sauer, H., Engel, S., Milosevic, N., Sharifpanah, F., Wartenberg, M."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 (2012): 501-508.
Chicago
Sauer, H., Engel, S., Milosevic, N., Sharifpanah, F., Wartenberg, M."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, no. 2 (2012): 501-508. https://doi.org/10.3892/ijo.2011.1230