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Src kinase is a direct target of apigenin against UVB-induced skin inflammation
Src kinase is a direct target of apigenin against UVB-induced skin inflammation
- Source :
- Carcinogenesis. 34(2)
- Publication Year :
- 2012
-
Abstract
- Apigenin, a flavonoid abundant in various vegetables and fruits, including parsley and onions, has been reported to possess anticarcinogenic effects. However, the direct molecular target of apigenin and its chemopreventive effect on ultraviolet (UV)-induced skin inflammation are not understood fully. Herein, we examined the anti-inflammatory effect of apigenin and its associated mechanisms in JB6 P+ cell line and SKH-1 hairless mouse model. Apigenin inhibited UVB-induced cyclooxygenase-2 (COX-2) expression, which is a well-known key mediator of inflammation and cancer, and restored the upstream stimulatory factor level in JB6 P+ cells. Immunoblot and kinase assay data demonstrate that Src activity was attenuated by apigenin, and this led to subsequent inhibition of UVB-induced phosphorylation of epidermal growth factor receptor, mitogen-activated protein kinases and Akt signaling. Inhibitory effects of apigenin on UVB-induced signaling were also confirmed in HaCaT human keratinocytes. In addition, in vitro pull-down assays revealed that apigenin binds Src in an adenosine triphosphate-competitive manner. Results using in vivo skin model indicate apigenin significantly inhibits UVB-induced ear edema development, COX-2 expression and Src kinase activity in SKH-1 hairless mice. Collectively, these findings suggest that apigenin exerts potent chemopreventive activity against UVB-induced skin inflammation primarily by targeting Src.
- Subjects :
- Keratinocytes
Cancer Research
Neoplasms, Radiation-Induced
Skin Neoplasms
Ultraviolet Rays
Immunoblotting
Dermatitis
chemistry.chemical_compound
Mice
Adenosine Triphosphate
Animals
Humans
Epidermal growth factor receptor
Apigenin
Phosphorylation
skin and connective tissue diseases
Luciferases
Promoter Regions, Genetic
Protein kinase B
Cells, Cultured
Mice, Hairless
integumentary system
biology
Chemistry
Kinase
General Medicine
Hairless
ErbB Receptors
HaCaT
src-Family Kinases
Cyclooxygenase 2
Cancer research
biology.protein
Female
Mitogen-Activated Protein Kinases
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 14602180
- Volume :
- 34
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Carcinogenesis
- Accession number :
- edsair.doi.dedup.....3fdacd8ffad076c5330a90c5de3b5fbf