Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts

Lim, Hyun; Park, Haeil; Kim, Hyun Pyo

doi:10.1016/j.bcp.2015.06.013

Cited by 152 publications

(88 citation statements)

References 46 publications

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“…4a; Fig. S2A-B, S3) as described (Coppe et al 2008, Lim et al 2015. This increase was reduced by apigenin in both strains to similar extents.…”

Section: Secretion Profile Of Apigenin-treated Senescent Cellssupporting

confidence: 68%

“…1b) and showed a similar dose response for BJ fibroblasts (Fig. S1A), also from neonatal foreskin, as described (Lim et al 2015). We used 10 μM apigenin for subsequent experiments.…”

Section: Suppression Of Il-6 Expression Upon Apigenin Treatmentmentioning

confidence: 55%

“…Apigenin was recently shown to reduce the secretion of several SASP factors in a human fibroblast strain induced to senesce by the clastogen bleomycin via the IRAK1/IκBα signaling pathway (Lim et al 2015). To determine how broadly apigenin suppresses the SASP, we analyzed its effects using several human fibroblast strains and senescence inducers, multiplex ELISAs, and several indicators of IL-1/IRAK/NF-κB signaling.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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 cellsstressed cells that accumulate with age in mammalsdisplay 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 epithelialmesenchymal 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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“…4a; Fig. S2A-B, S3) as described (Coppe et al 2008, Lim et al 2015. This increase was reduced by apigenin in both strains to similar extents.…”

Section: Secretion Profile Of Apigenin-treated Senescent Cellssupporting

confidence: 68%

“…1b) and showed a similar dose response for BJ fibroblasts (Fig. S1A), also from neonatal foreskin, as described (Lim et al 2015). We used 10 μM apigenin for subsequent experiments.…”

Section: Suppression Of Il-6 Expression Upon Apigenin Treatmentmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…Further analysis revealed that NF-κBIZ co-localized with infiltrating macrophages in old rats, indicating that NF-κBIZ elevation during aging is associated with increased macrophage invasion. Interestingly, NF-κBIZ up-regulation was recently reported in a senescent-associated secretory fibroblast phenotype and blocking NF-κBIZ activation prevented senescence [30]. Since senescent-associated cytokines and macrophages play pivotal roles in the regulation of renal inflammation and aging, these findings hint at the physiological meaning of the up-regulations of NF-κBIZ at the transcription and protein levels in aged rat kidneys, and place focus on its pathophysiological role in macrophages.…”

Section: Discussionmentioning

confidence: 89%

Involvement of NF-κBIZ and related cytokines in age-associated renal fibrosis

et al. 2017

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Chronic inflammation is a major contributor to age-related nephropathic changes, including renal fibrosis. In this study, various experimental paradigms were designed to delineate the role played by NF-?BIZ (also known as I?B?) in age-associated renal fibrosis. Analyses based on RNA-sequencing findings obtained by next generation sequencing (NGS) revealed the upregulations of NF-?BIZ and of IL-6 and MCP-1 (both known to be regulated by NF-?BIZ) during aging. The up-regulation of NF-?BIZ in aged rat kidneys coincided with increased macrophage infiltration. In LPS-treated macrophages, oxidative stress was found to play a pivotal role in NF-?BIZ expression, suggesting age-related oxidative stress is associated with NF-?BIZ activation. Furthermore, these in vitro findings were confirmed in LPS-treated old rats, which showed higher levels of oxidative stress and NF-?BIZ in kidneys than LPS-treated young rats. Additional in vitro experiments using macrophages and kidney fibroblasts demonstrated NF-?BIZ and related cytokines participate in fibrosis. In particular, increased levels of NF-?BIZ-associated cytokines in macrophages significantly up-regulated TGF-β induced kidney fibroblast activation. Moreover, experiments with NF-?BIZ knocked down macrophages showed reduced TGF-β- induced kidney fibroblast activation. The findings of the present study provide evidence regarding an involvement of NF-?BIZ in age-associated progressive renal fibrosis and provides potential targets for its prevention.

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“…Chronic resveratrol treatment also dampens the SASP [30], likely through its ability to decrease IκB kinase activity, which leads to decreased IκBα phosphorylation and subsequent NF-κB activation [31]. Other natural compounds, such as apigenin, wogonin, and kaempferol, inhibit the SASP by blocking IκBζ expression and reducing NF-κB activity [32]. …”

Section: Eliminating Senescent Cellsmentioning

confidence: 99%

Targeting Senescent Cells: Possible Implications for Delaying Skin Aging: A Mini-Review

Velarde

Demaria

2016

Gerontology

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Senescent cells are induced by a wide variety of stimuli. They accumulate in several tissues during aging, including the skin. Senescent cells secrete proinflammatory cytokines, chemokines, growth factors, and proteases, a phenomenon called senescence-associated secretory phenotype (SASP), which are thought to contribute to the functional decline of the skin as a consequence of aging. Due to the potential negative effects of the SASP in aged organisms, drugs that selectively target senescent cells represent an intriguing therapeutic strategy to delay aging and age-related diseases. Here, we review studies on the role of senescent cells in the skin, with particular emphasis on the age-related mechanisms and phenotypes associated with excessive accumulation of cellular senescence. We discuss the aberrant behavior of senescent cells in aging and how the different signaling pathways associated with survival and secretion of senescent cells can be engaged for the development of targeted therapies.

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Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts

Cited by 152 publications

References 46 publications

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

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

Involvement of NF-κBIZ and related cytokines in age-associated renal fibrosis

Targeting Senescent Cells: Possible Implications for Delaying Skin Aging: A Mini-Review

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