The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Self-citationAging, Cellular Senescence, and Cancer
Campisi, J. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183653 · Cited by 2,954 · cited 2×
“However, because senescent cells accumulate with age, their chronic presence—most likely through the SASP—can drive age-related pathologies, including, ironically, cancer (Campisi 2013, Muñoz-Espín and Serrano 2014, Baker et al. 2016).”
BackgroundSelf-citationNaturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
Geroscience: Linking Aging to Chronic Disease
Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.039 · Cited by 2,764
Self-citationPersistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232
Self-citationD IETARY F LAVONOIDS : Bioavailability, Metabolic Effects, and Safety
Ross, J. A., & Kasum, C. M. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.111401.144957 · Cited by 2,153
NF-κB, Inflammation, and Metabolic Disease
Baker, R. G., Hayden, M. S., & Ghosh, S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2010.12.008 · Cited by 1,952
Research works printed but not linked: 1
- Funakoshi-Tago M, Nakamura K, Tago K, Mashino T, Kasahara T (2011b) Anti-inflammatory activity of structurally related flavonoids, apigenin, luteolin and fisetin. Int Immunopharmacol 11:1150–1159 · DOI
Cited by
Sorted by citations
The senescence-associated secretory phenotype and its physiological and pathological implications
Wang, B., Han, J., Elisseeff, J. H., & Demaria, M. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00727-x · Cited by 948
Cardoso, A. L., Fernandes, A. M. A., Aguilar‐Pimentel, J. A., de Angelis, M. H., Guedes, J. R., Brito, M. A., Ortolano, S., Pani, G., Athanasopoulou, S., Gonos, E. S., et al. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.07.004 · Cited by 483
The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice
Xu, Q., Fu, Q., Li, Z., Liu, H., Wang, Y., Lin, X., He, R., Zhang, X., Ju, Z., Campisi, J., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00491-8 · Cited by 341
Self-citationTargeting senescent cells in translational medicine
Paez‐Ribes, M., González‐Gualda, E., Doherty, G. J., & Muñoz‐Espín, D. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201810234 · Cited by 293
Aging of the cells: Insight into cellular senescence and detection Methods.
Mohamad Kamal, N. S., Safuan, S., Shamsuddin, S., & Foroozandeh, P. (2020) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2020.151108 · Cited by 287
Metadata
- 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 (medical) › Flavonoids in Medical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Biochemistry (medical) › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
