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Addition of 2-deoxyglucose enhances growth inhibition but reverses acidification in colon cancer cells treated with phenformin.

Abstract
A report that effects of butyrate on some cells may be mediated by activation of AMP-activated protein kinase (AMPK) prompted this study which examines if other AMPK activators can induce differentiation and inhibit proliferation of colon cancer cells in a manner similar to butyrate. Using induction of alkaline phosphatase as a marker, it was observed that compound C, an AMPK inhibitor, is able to reduce the differentiating effect of butyrate on SW1116 and Caco-2 colon cancer cells. Metformin was observed to be less effective than butyrate in the induction of alkaline phosphatase but was more effective as a growth inhibitor. Phenformin was found to be a more potent growth inhibitor than metformin and both compounds cause acidification of the medium when incubated with colon cancer cells. Combined incubation of 2-deoxyglucose with either of the biguanides prevented the acidification of the medium but enhanced the growth inhibitory effects.
AuthorsMichael A Lea, Jerel Chacko, Sandhya Bolikal, Ji Y Hong, Ryan Chung, Andres Ortega, Charles desbordes
JournalAnticancer research (Anticancer Res) Vol. 31 Issue 2 Pg. 421-6 (Feb 2011) ISSN: 1791-7530 [Electronic] Greece
PMID21378320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Butyrates
  • Deoxyglucose
  • Phenformin
  • Adenylate Kinase
  • Alkaline Phosphatase
Topics
  • Adenylate Kinase (metabolism)
  • Alkaline Phosphatase (biosynthesis, metabolism)
  • Antineoplastic Combined Chemotherapy Protocols (pharmacology)
  • Butyrates (pharmacology)
  • Caco-2 Cells
  • Cell Growth Processes (drug effects)
  • Colonic Neoplasms (drug therapy, enzymology, pathology)
  • Deoxyglucose (administration & dosage, pharmacology)
  • Drug Synergism
  • Enzyme Activation (drug effects)
  • Enzyme Induction (drug effects)
  • HT29 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Phenformin (administration & dosage, pharmacology)

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