• Open Access

Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation


  • While this paper was on review, Struhl and colleagues published that metformin inhibits the expression of genes coding for inflammatory cytokines in breast cancer stem cells via inhibition of NF-κB (doi: 10.1073/pnas.1221055110), Hirsch HA, Iliopoulos D, Struhl K (2013). Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci U S A 110: 972–977.


Gerardo Ferbeyre, Département de Biochimie, Université de Montréal, Pavillon Roger-Gaudry 2900 boul. Édouard Montpetit, Montréal, QC, H3C 3J7, Canada. Tel.: 1-514 343 7571; fax: 1-514 343 2210; e-mail: g.ferbeyre@umontreal.ca and

Michael N. Pollak, Division of Experimental Medicine, McGill University and Segal Cancer Centre of Jewish General Hospital, 3755 Côte Ste Catherine, Montréal, QC, H3T 1E2, Canada. Tel.: 1-514 340 8302; fax: 1-514 340 8302; e-mail: michael.pollak@mcgill.ca


We show that the antidiabetic drug metformin inhibits the expression of genes coding for multiple inflammatory cytokines seen during cellular senescence. Conditioned medium (CM) from senescent cells stimulates the growth of prostate cancer cells but treatment of senescent cells with metformin inhibited this effect. Bioinformatic analysis of genes downregulated by metformin suggests that the drug blocks the activity of the transcription factor NF-κB. In agreement, metformin prevented the translocation of NF-κB to the nucleus and inhibited the phosphorylation of IκB and IKKα/β, events required for activation of the NF-κB pathway. These effects were not dependent on AMPK activation or on the context of cellular senescence, as metformin inhibited the NF-κB pathway stimulated by lipopolysaccharide (LPS) in ampk null fibroblasts and in macrophages. Taken together, our results provide a novel mechanism for the antiaging and antineoplastic effects of metformin reported in animal models and in diabetic patients taking this drug.