Premium
Photophysical studies on melatonin and its receptor agonists
Author(s) -
Roberts Joan E.,
Hu DanNing,
Martinez Lydia,
Chignell Colin F.
Publication year - 2000
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2000.290205.x
Subject(s) - melatonin , melatonin receptor , receptor , agonist , medicine , endocrinology , chemistry , pharmacology , biology
Previous work has demonstrated that melatonin inhibits the growth of both dermal and uveal melanoma cells. Recent clinical trials have found that melatonin is an efficacious treatment for metastatic dermal melanoma. The goal of this study was to provide further insight into the oncostatic mechanism(s) of melatonin. The inhibition of the growth of uveal melanoma cells is dose‐dependent (0.1–10 nM) within the range of endogenous melatonin concentrations (2 nM) found in the human aqueous humor. We know that this inhibition of growth is receptor‐mediated, at least in part, because uveal melanoma cell growth was also blocked by the agonists of melatonin receptors. There are two known membrane receptors for melatonin (Mel 1a and Mel 1b ) and one known nuclear receptor (Mel 2 ). To determine if singlet oxygen production and/or quenching contributed to the growth inhibition of melatonin, we examined the photophysical properties of melatonin and its agonists. Using flash photolysis, we determined that melatonin and its membrane receptor agonist 6‐chloromelatonin (Mel 1a‐b , Lilly, Indianapolis, IN) produced very little singlet oxygen (ϕ Δ =0.073 and ϕ Δ =0.01, respectively). There was no detectable singlet oxygen phosphorescence at 1,270 nm for the nuclear receptor agonist CG‐52608 (Mel 2 , Novartis, Basel, Switzerland). In contrast, the agonist of the Mel 1b receptor, S‐20098 (Servier, Paris, France), produced singlet oxygen with a quantum efficiency of ϕ Δ =0.34. Singlet oxygen was quenched by melatonin and 6‐chloromelatonin at approximately the same rate (6.1×10 7 M −1 s −1 and 6.0×10 7 M −1 s −1 in CD 3 OD), while the rate of quenching for the nuclear receptor agonist CG‐52608 and membrane receptor agonist S‐20098 was less (2.2×10 7 M −1 s −1 and 1.5×10 7 M −1 s −1 , respectively). It appears that the production of singlet oxygen by melatonin would not be sufficient to directly block the proliferation of melanoma cells, but may activate gene products that could contribute to the oncostatic effect.