Open AccessMetformin inhibits the senescence‐associated secretory phenotype by interfering with IKK / NF ‐κ B activation
Author(s) -
Moiseeva Olga,
DeschênesSimard Xavier,
StGermain Emmanuelle,
Igelmann Sebastian,
Huot Geneviève,
Cadar Alexandra E.,
Bourdeau Véronique,
Pollak Michael N.,
Ferbeyre Gerardo
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12075
Subject(s) - metformin , ampk , senescence , biology , nf κb , proinflammatory cytokine , iκb kinase , lipopolysaccharide , pharmacology , amp activated protein kinase , microbiology and biotechnology , phosphorylation , cancer research , signal transduction , inflammation , endocrinology , immunology , protein kinase a , diabetes mellitus
Summary 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 ‐κ B . In agreement, metformin prevented the translocation of NF ‐κ B to the nucleus and inhibited the phosphorylation of I κ B and IKK α/β, events required for activation of the NF ‐κ B pathway. These effects were not dependent on AMPK activation or on the context of cellular senescence, as metformin inhibited the NF ‐κ B 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.