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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-9-2
pubmed:abstractText
AMP-activated protein kinase (AMPK), a highly conserved protein in eukaryotes, functions as a major metabolic switch to maintain energy homeostasis. It also intrinsically regulates the mammalian cell cycle. Moreover, the AMPK cascade has emerged as an important pathway implicated in cancer control. In this study we investigated the effects of curcumin on apoptosis and the regulatory effect of the AMPK-cyclooxygenase-2 (COX-2) pathway in curcumin-induced apoptosis. Curcumin has shown promise as a chemopreventive agent because of its in vivo regression of various animal-model colon cancers. This study focused on exploiting curcumin to apply antitumorigenic effects through modulation of the AMPK-COX-2 cascade. Curcumin exhibited a potent apoptotic effect on HT-29 colon cancer cells at concentrations of 50 micromol/L and above. These apoptotic effects were correlated with the decrease in pAkt and COX-2, as well as the increase in p-AMPK. Cell cycle analysis showed that curcumin induced G(1)-phase arrest. Further study with AMPK synthetic inhibitor Compound C has shown that increased concentrations of Compound C would abolish AMPK expression, accompanied by a marked increase in COX-2 as well as pAkt expression in curcumin-treated HT-29 cells. By inhibiting AMPK with Compound C, we found that curcumin-treated colon cancer cells were no longer undergoing apoptosis; rather, they were proliferative. These results indicate that AMPK is crucial in apoptosis induced by curcumin and further that the pAkt-AMPK-COX-2 cascade or AMPK-pAkt-COX-2 pathway is important in cell proliferation and apoptosis in colon cancer cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1749-6632
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-94
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19723094-AMP-Activated Protein Kinases, pubmed-meshheading:19723094-Antineoplastic Agents, pubmed-meshheading:19723094-Apoptosis, pubmed-meshheading:19723094-Blotting, Western, pubmed-meshheading:19723094-Cell Cycle, pubmed-meshheading:19723094-Cell Proliferation, pubmed-meshheading:19723094-Cell Survival, pubmed-meshheading:19723094-Colonic Neoplasms, pubmed-meshheading:19723094-Curcumin, pubmed-meshheading:19723094-Cyclooxygenase 2, pubmed-meshheading:19723094-Dose-Response Relationship, Drug, pubmed-meshheading:19723094-Enzyme Activation, pubmed-meshheading:19723094-G1 Phase, pubmed-meshheading:19723094-HT29 Cells, pubmed-meshheading:19723094-Humans, pubmed-meshheading:19723094-Proto-Oncogene Proteins c-akt, pubmed-meshheading:19723094-Pyrazoles, pubmed-meshheading:19723094-Pyrimidines, pubmed-meshheading:19723094-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Regulatory effect of the AMPK-COX-2 signaling pathway in curcumin-induced apoptosis in HT-29 colon cancer cells.
pubmed:affiliation
Department of Food and Nutrition, Hannam University Daedeok Valley Campus, Yuseong-gu, Daejeon, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't