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Geroscience. 2017 Apr;39(2):161-173. doi: 10.1007/s11357-017-9970-1. Epub 2017 Apr 4.

Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells.

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Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA.
California Pacific Medical Center Research Institute, 475 Brannan Street, San Francisco, CA, 94107, USA.
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA.
Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA.


Apigenin (4',5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cells-stressed cells that accumulate with age in mammals-display a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin. Here, we confirm that apigenin suppresses the SASP in three human fibroblast strains induced to senesce by ionizing radiation, constitutive MAPK (mitogen-activated protein kinase) signaling, oncogenic RAS, or replicative exhaustion. Apigenin suppressed the SASP in part by suppressing IL-1α signaling through IRAK1 and IRAK4, p38-MAPK, and NF-κB. Apigenin was particularly potent at suppressing the expression and secretion of CXCL10 (IP10), a newly identified SASP factor. Further, apigenin-mediated suppression of the SASP substantially reduced the aggressive phenotype of human breast cancer cells, as determined by cell proliferation, extracellular matrix invasion, and epithelial-mesenchymal transition. Our results support the idea that apigenin is a promising natural product for reducing the impact of senescent cells on age-related diseases such as cancer.


Flavonoids; Human fibroblasts; IL-1A; IL-6; IRAK1/4; Invasion; NF-κB; Proliferation

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