Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis

Andrew J. O'Brien, Linda A. Villani, Lindsay A. Broadfield, Vanessa P. Houde, Sandra Galic, Giovanni Blandino, Bruce E. Kemp, Theodoros Tsakiridis, Paola Muti, Gregory R. Steinberg

Research output: Contribution to journalArticle

Abstract

Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, amechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin (

Original languageEnglish
Pages (from-to)177-187
Number of pages11
JournalBiochemical Journal
Volume469
Issue number2
DOIs
Publication statusPublished - Jul 15 2015

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

O'Brien, A. J., Villani, L. A., Broadfield, L. A., Houde, V. P., Galic, S., Blandino, G., Kemp, B. E., Tsakiridis, T., Muti, P., & Steinberg, G. R. (2015). Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis. Biochemical Journal, 469(2), 177-187. https://doi.org/10.1042/BJ20150122