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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apigenin / pharmacology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Cellular Senescence / drug effects*
  • Cellular Senescence / physiology
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Interleukin-1alpha / metabolism
  • Interleukin-6 / metabolism
  • NF-kappa B / metabolism
  • Phenotype
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Interleukin-1alpha
  • Interleukin-6
  • NF-kappa B
  • Apigenin
  • IRAK1 protein, human
  • IRAK4 protein, human
  • Interleukin-1 Receptor-Associated Kinases
  • p38 Mitogen-Activated Protein Kinases