Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells
Open accessAbstract
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.
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Beside antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, making them of interest as anti-aging compounds.
“Beside the antioxidant activity, flavonoids have anti-inflammatory, vasodilator, anticoagulant, cardioprotective, anti-diabetic, neuroprotective, and anti-obesity activities, which make them of great interest as anti-aging compounds (Table 3) [228,229,230,231,232,233,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [237]
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- Authors
- Perrott, K. M., Wiley, C. D., Desprez, P.-Y., & Campisi, J.
- Affiliations
- Buck Institute for Research on Aging (US)
- California Pacific Medical Center (US)
- Corresponding author
- Campisi, Judith
- Venue
- GeroScience
- Published
- 2017-04
- Volume
- 39
- Issue
- 2
- Pages
- 161-173
- ISSN
- 2152-4041 (ISSN-L)
- 2509-2715
- 2509-2723
- PMC
- PMC5411372
- OpenAlex
- W2604407819
- Cited by
- 163
- References
- 42
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 28 · 2023: 18 · 2022: 17 · 2021: 19 · 2020: 22 · 2019: 15 · 2018: 10 · 2017: 5
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- GeroScience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- SENS Research Foundation (BC2010)
- National Institute on Aging (AG009909, AG017242)
- Topics
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- apigenin, senescence-associated secretory phenotype, cellular senescence, flavonoids, breast cancer, IRAK1, IRAK4, p38 MAPK, NF-κB, CXCL10, paracrine effects, replicative senescence, oncogenic Ras, MAPK signaling, extracellular matrix invasion, epithelial-mesenchymal transition, inflammation, aging
- MeSH terms
- Breast Neoplasms, Female, Fibroblasts, Humans, Phenotype, Signal Transduction, Interleukin-6, NF-kappa B, Cellular Senescence, Cell Culture Techniques, Apigenin, p38 Mitogen-Activated Protein Kinases, Cell Proliferation, Interleukin-1alpha, Interleukin-1 Receptor-Associated Kinases
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