Abstract
The present study aims to determine the effect of AMPK on etoposide-induced apoptosis of cancer cells. Our results revealed that etoposide induced AMPK activation in prostate C4-2 cancer cells, an event that was attenuated by ATM siRNA. In A549 cells that lack LKB1, AMPK was unable to be activated by etoposide, which was restored by introduction of LKB1. Likewise, silencing LKB1 in C4-2 cells impaired AMPK activation. Finally, etoposide displayed a potent pro-apoptotic effect in cancer cells with functional LKB1 and AMPK. Thus, our results establish a linear relationship of ATM, LKB1 and AMPK in response to the DNA damage drug.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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AMP-Activated Protein Kinase Kinases
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AMP-Activated Protein Kinases / metabolism*
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects*
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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DNA-Binding Proteins / metabolism*
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Enzyme Activation
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Etoposide / pharmacology*
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Humans
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Male
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / metabolism
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Protein Serine-Threonine Kinases / metabolism*
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Tumor Suppressor Proteins / metabolism*
Substances
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Antineoplastic Agents, Phytogenic
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Cell Cycle Proteins
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DNA-Binding Proteins
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Tumor Suppressor Proteins
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Etoposide
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases
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STK11 protein, human
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AMP-Activated Protein Kinase Kinases
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AMP-Activated Protein Kinases