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

Aging Cell

Olga Moiseeva²  Xavier Deschênes-Simard²  Emmanuelle St-Germain²  Sebastian Igelmann²  Geneviève Huot²  Alexandra E. Cadar²  Véronique Bourdeau²  Michael N. Pollak¹ 

[1] Division of Experimental Medicine, McGill University and Segal Cancer Centre of Jewish General Hospital, Montréal, QC, Canada;Département de Biochimie, Université de Montréal, Montréal, QC, Canada

关键词: cellular senescence;    cytokines;    metformin;    NF‐κB;    senescence;   

DOI  :  10.1111/acel.12075

来源: Wiley

【 摘 要 】

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-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.

【 授权许可】

Unknown   
© 2013 John Wiley & Sons Ltd and the Anatomical Society