Ultraviolet (UV) radiation is the primary environmental risk factor in the development of nonmelanoma
skin cancer, and UVB in particular promotes
tumor growth through various signaling pathways.
Kaempferol, a
flavonoid with anti-inflammatory and anti-oxidative properties, has been studied as a chemopreventive agent; however, little is known regarding its effects on UVB-induced photo-
carcinogenesis. Here, we examined the effect of
kaempferol on UVB-induced skin
inflammation. We found that
kaempferol suppressed UVB-induced
cyclooxygenase-2 (COX-2)
protein expression in mouse skin epidermal JB6 P+ cells and attenuated the UVB-induced transcriptional activities of cox-2 and
activator protein-1 (AP-1).
Kaempferol attenuated the UVB-induced phosphorylation of several
mitogen-activated protein kinases (MAPKs), including ERKs, p38, and JNKs, but had no effect on the phosphorylation of the upstream MAPK regulator Src. However, in vitro and ex vivo
kinase assays demonstrated that
kaempferol suppressed
Src kinase activity. Furthermore, in vivo data from mouse skin support the idea that
kaempferol suppresses UVB-induced COX-2 expression by blocking
Src kinase activity. A pull-down assay revealed that
kaempferol competes with
ATP for direct binding to Src. Docking data suggest that
kaempferol docks easily into the
ATP-binding site of Src, which is located between the N and the C lobes of the
kinase domain. Taken together, these results suggest that
kaempferol is a potent chemopreventive agent against
skin cancer through its inhibitory interaction with Src.