Effects of a melanogenic bicyclic monoterpene diol on cell cycle, p53, TNF-alpha, and PGE2 are distinct from those of UVB.
| Autor: | Kraus E; AGI Dermatics, 205 Buffalo Avenue, Freeport, NY 11520, USA., Galvin JW, Boumakis S, Boamah EK, Canning MT, Yarosh DB, Brown DA |
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| Jazyk: | angličtina |
| Zdroj: | Photodermatology, photoimmunology & photomedicine [Photodermatol Photoimmunol Photomed] 2003 Dec; Vol. 19 (6), pp. 295-302. |
| DOI: | 10.1046/j.1600-0781.2003.00061.x |
| Abstrakt: | Purpose: Bicyclic monoterpene (BMT) diols are small-molecule compounds that mimic ultraviolet radiation (UVR) by inducing melanogenesis. The objective of this study was to compare the effects of 2,2-dimethyl-3-propanyldiol-norbornane (AGI-1140), a novel BMT diol, and ultraviolet B (UVB) on additional cellular responses. Methods: S91 mouse melanoma cells were treated with a range of concentrations of AGI-1140, and examined for induction of melanogenesis and nitric oxide (NO). The effect of AGI-1140 on dendrite outgrowth from human melanocytes was examined by quantitative microscopy. The effect of AGI-1140 and UVB on phosphorylation of p53 serine 15 in human keratinocytes was examined by Western blotting, while the release of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) was determined by enzyme-linked immunosorbent assay. The effects of AGI-1140 and UVB on cell cycle arrest of human melanocytes, keratinocytes, fibroblasts, and endothelial cells were compared using fluorescence-activated cell sorting. Results: Similar to UVB, AGI-1140 induced both melanogenesis and NO in melanoma cells. AGI-1140 also induced dendrite outgrowth from melanocytes, indicative of differentiation. However, whereas UVB induced G2 cell cycle arrest with phosphorylation of p53 at serine 15, AGI-1140 induced G1 cell cycle arrest without this phosphorylation. Additionally, unlike UVB, AGI-1140 did not increase the secretion of TNF-alpha or PGE2, mediators of UVB-induced immunosuppressive and inflammatory responses in the skin that may contribute to carcinogenesis. Conclusion: This study shows that melanogenesis can be induced by AGI-1140 without many of the deleterious effects associated with UVB. |
| Databáze: | MEDLINE |
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