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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.

Author information

1
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA.
2
California Pacific Medical Center Research Institute, 475 Brannan Street, San Francisco, CA, 94107, USA.
3
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA. jcampisi@buckinstitute.org.
4
Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA. jcampisi@buckinstitute.org.

Abstract

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.

KEYWORDS:

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

PMID:
28378188
PMCID:
PMC5411372
DOI:
10.1007/s11357-017-9970-1
[Indexed for MEDLINE]
Free PMC Article

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