Research Perspective Volume 3, Issue 11 pp 1063—1077

Metformin and the ATM DNA damage response (DDR): Accelerating the onset of stress-induced senescence to boost protection against cancer


Figure 3. Chronic exposure to metformin accelerates the onset of replicative senescence in human [WI-38 and BJ-1] fibroblast cultures confirmed by senescence-associated β-galactosidase (SA-β-gal) staining (A). Chronic exposure to metformin sensitizes [MCF-7] cancer cells to the senescence program activated by the DNA-damaging drug doxorubicin (B). Chronic exposure to metformin transcriptionally activates a senescence-associated secretory phenotype (SASP) or senescence messaging secretome (SMS) involving the production of factors that reinforce the senescence arrest, alter the surrounding microenvironment, and trigger immune surveillance of the senescent cells.