Abstract:
:AMPK has been termed the fuel sensor of mammalian cells because it directly responds to the depletion of the fuel molecule ATP. In previous work, we found that AMPK is strongly activated by tumor-like hypoxia and glucose deprivation, independently of the oxygen response system associated with HIF-1. We also observed high levels of AMPK activity in tumor cells in vivo, using different model tumors. These findings suggested the hypothesis that modulation of AMPK activity could have therapeutic value for the treatment of solid tumors. To investigate this hypothesis, we have been conducting a SAR study of potential small-molecule modulators of AMPK activity. Here we report that the chemotherapeutic drug SU11248 (sunitinib) is at least as potent an inhibitor of AMPK as compound C, which is a commonly used experimental direct inhibitor of the enzyme. We also provide a computational model of the binding pose of SU11248 to an AMPKα subunit, which suggests a structural basis for the affinity of the drug for the ATP site of the catalytic domain. The ability of SU11248 to inhibit AMPK has potential clinical significance--there may be populations of SU11248-treated patients in which AMPK activity is inhibited in normal as well as in tumor tissue.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Laderoute KR,Calaoagan JM,Madrid PB,Klon AE,Ehrlich PJdoi
10.4161/cbt.10.1.12162subject
Has Abstractpub_date
2010-07-01 00:00:00pages
68-76issue
1eissn
1538-4047issn
1555-8576pii
12162journal_volume
10pub_type
杂志文章abstract:BACKGROUND AND AIM:Widespread applicability of tissue-based mRNA expression screening for Barrett esophagus (BE) is likely to require (1) accurate methods for assaying archival formalin-fixed, paraffin-embedded (FFPE) histopathology specimens taken at endoscopy, and (2) validation studies of promising biomarkers in dif...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.2.12166
更新日期:2010-07-15 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.2.10287
更新日期:2010-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.4.10.2195
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abstract::Understanding the biology of breast cancer stem cells and trying new ways to obliterate these cells would be a key step in developing cures for breast cancer. The objective of this study was to investigate the effect of mutant TNFalpha on human breast cancer stem cells derived from MCF7 cell line under the characteriz...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.9.4885
更新日期:2007-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
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更新日期:2007-01-01 00:00:00
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journal_title:Cancer biology & therapy
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abstract::Although daunomycin and adriamycin are considered effective antitumor drugs and have been used in the clinic for over 40 years, their mechanism of action is still a matter of debate. We investigated the influence of daunomycin on interaction between linker or core histones and DNA in live HeLa cells in vitro, using im...
journal_title:Cancer biology & therapy
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更新日期:2013-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.3.785
更新日期:2004-03-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.7.6172
更新日期:2008-07-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.11.6837
更新日期:2008-11-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.19.9650
更新日期:2009-10-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2013-08-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,随机对照试验
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更新日期:2006-10-01 00:00:00
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更新日期:2013-07-01 00:00:00
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journal_title:Cancer biology & therapy
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doi:
更新日期:2009-03-15 00:00:00
abstract:BACKGROUND INFORMATION:Previous studies have revealed that leptin may be involved in epithelial-mesenchymal transition (EMT), a crucial initiator of cancer progression to facilitate metastatic cascade, increase tumor recurrence, and ultimately cause poor prognosis. However, the underlying mechanism remains unclear. The...
journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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更新日期:2013-06-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
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更新日期:2014-05-01 00:00:00
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journal_title:Cancer biology & therapy
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更新日期:2009-02-01 00:00:00
abstract::The mitochondrial production of reactive oxygen species has been implicated in the anticancer activity of furanonaphthoquinone. However, the mechanism of the activation remains elusive. In the current study, we found that treatment of HeLa cells with 2-methyl-5(or -8)-hydroxy-furanonaphthoquinone (FNQ13) induces mitoc...
journal_title:Cancer biology & therapy
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doi:10.4161/cbt.5.11.3302
更新日期:2006-11-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.9.8186
更新日期:2009-05-01 00:00:00
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journal_title:Cancer biology & therapy
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更新日期:2019-01-01 00:00:00
abstract::MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Genes encoding miRNAs are located in regions of the genome that are commonly amplified, deleted or rearranged. They are commonly dysregulated in human cancers and known to act as oncogenes ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.10.3.12548
更新日期:2010-08-01 00:00:00
abstract::Prostate cancer is the second leading cause of cancer-related deaths in men. Fatty acid synthase (FASN) is normally upregulated during human prostate cancer onset and metastatic progression and its expression positively correlates with the development of advanced metastatic disease. However, it remains unknown what mo...
journal_title:Cancer biology & therapy
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doi:10.4161/cbt.6.8.4447
更新日期:2007-08-01 00:00:00