title: Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells.
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.
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Perrott
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Wiley
authors.affiliation: California Pacific Medical Center Research Institute, 475 Brannan Street, San Francisco, CA, 94107, USA.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Desprez
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA. jcampisi@buckinstitute.org.|Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA. jcampisi@buckinstitute.org.
authors.forename: Judith
authors.initials: J
authors.lastname: Campisi
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053582:Interleukin-1alpha; D015850:Interleukin-6; D016328:NF-kappa B; D047310:Apigenin; C507768:IRAK1 protein, human; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Flavonoids; Human fibroblasts; IL-1A; IL-6; IRAK1/4; Invasion; NF-κB; Proliferation