3-7-4--trihydroxyflavone and Skin-Neoplasms

3-7-4--trihydroxyflavone has been researched along with Skin-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for 3-7-4--trihydroxyflavone and Skin-Neoplasms

ArticleYear
5-deoxykaempferol plays a potential therapeutic role by targeting multiple signaling pathways in skin cancer.
    Cancer prevention research (Philadelphia, Pa.), 2010, Volume: 3, Issue:4

    Nontoxic small molecules with multitargeting effects are believed to have potential in cancer prevention. Dietary phytochemicals were shown to exhibit cancer-preventive effects attributed to their antioxidant capacities. In this report, we show that the natural compound 5-deoxykaempferol (5-DK) exerts a chemopreventive effect on UVB-induced skin carcinogenesis by targeting multiple signaling molecules. 5-DK suppressed the UVB-induced expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor in mouse skin epidermal JB6 P+ cells. Moreover, 5-DK inhibited phosphorylation of MKK3/6, MKK4, and Akt, but had no effect on phosphorylation of Src, extracellular signal-regulated kinases, or ribosomal S6 kinase (RSK). However, 5-DK affected multiple targets by reducing Src, phosphoinositide 3-kinase (PI3K), and RSK2 activities. In particular, pull-down assays revealed that 5-DK specifically bound to and competed with ATP for binding with Src, PI3K, and RSK2. Exposure to 5-DK significantly suppressed UVB-induced tumorigenesis in mouse skin in a dose-dependent manner, and it inhibited the UVB-induced expression of COX-2, proliferating cell nuclear antigen, vascular endothelial growth factor, and matrix metalloproteinase-9. Our data suggest that 5-DK docks at the ATP-binding site of Src, PI3K, and RSK2. For RSK2, the ATP-binding site is located between the N- and C-lobes of the kinase domain. Taken together, our results indicate that 5-DK holds promise for the treatment of UVB-induced skin cancer by targeting Src, PI3K, and RSK2 signaling.

    Topics: Animals; Antineoplastic Agents; Blotting, Western; Cyclooxygenase 2; Fabaceae; Flavonoids; Gene Expression; Immunohistochemistry; Kaempferols; Mice; Mice, Hairless; Phosphatidylinositol 3-Kinases; Phytotherapy; Plant Extracts; Ribosomal Protein S6 Kinases, 90-kDa; Signal Transduction; Skin Neoplasms; src-Family Kinases; Vascular Endothelial Growth Factor A

2010