Effects of a melanogenic bicyclic monoterpene diol on cell cycle, p53, TNF-alpha, and PGE2 are distinct from those of UVB.

Abstract

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.

• Authors: Eliyahu Kraus, Jason W Galvin, Stavroula Boumakis, Ernest K Boamah, Matthew T Canning, Daniel B Yarosh, David A Brown
• Journal: Photodermatology, photoimmunology & photomedicine (Photodermatol Photoimmunol Photomed) Vol. 19 Issue 6 Pg. 295-302 (Dec 2003) ISSN: 0905-4383 [Print] England
• PMID: 14617104 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,2-dimethyl-3-propanyldiol-norbornane
• Monoterpenes
• Norbornanes
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Dinoprostone

Topics

• Animals
• Blotting, Western
• Cell Cycle (drug effects, radiation effects)
• Cell Line, Tumor (drug effects, metabolism, radiation effects)
• Dendrites (drug effects, metabolism, radiation effects)
• Dinoprostone (biosynthesis)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, metabolism, radiation effects)
• Enzyme-Linked Immunosorbent Assay
• Fibroblasts (drug effects, metabolism, radiation effects)
• Keratinocytes (drug effects, metabolism, radiation effects)
• Melanocytes (drug effects, metabolism, radiation effects)
• Melanoma, Experimental (pathology)
• Mice
• Monoterpenes (administration & dosage, pharmacology)
• Nitric Oxide (biosynthesis)
• Norbornanes (administration & dosage, pharmacology)
• Skin Pigmentation (drug effects, radiation effects)
• Tumor Necrosis Factor-alpha (biosynthesis)
• Ultraviolet Rays