Evidence for Biphasic Effects and Differential Expression of Melatonin (MLT) Receptors in Oral Squamous Cell Carcinomas

Abstract

Objectives: Previous work from this group has demonstrated that melatonin (MLT) is capable of significantly altering the growth and viability of oral cancer cell lines. The objective of this study was to explore the receptors that may modulate MLT effects in oral cancers.

Methods: Polymerase Chain Reaction (PCR) primers specific for the primary, cell-surface MLT receptors (MT1 & MT2) were obtained and used to analyze the mRNA expression in CAL27, SCC15 and SCC25 oral cancer cell lines. Extracted RNA following MLT administration was also analyzed.

Results: Expression of the primary MLT receptor MT1 was absent in all cell lines, although expression of the secondary receptor (MT2) was observed. MLT administration within the physiologic range was sufficient to induce MT1 expression in all cell lines, suggesting the MT2 receptor may initially facilitate this process. Saturation of both MT1 and MT2 receptors observed within the supraphysiologic ranges correlated with the induction of apoptosis-related caspase signaling and the activation of the intranuclear MLT receptor RZR.

Conclusions: This may be the first study to demonstrate the down-regulation of MT1 mRNA in oral cancers, as well as novel evidence of the specific role of melatonin and the cognate receptors in modulating oral cancer growth.

 

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