An Exploratory Study of High-Concentration Trace Amine Effects and Adrenoceptor Expression Patterns in SH-SY5Y Cells...

The antitumoral activity of monoamine receptor ligands appears to be important as a potential approach to cancer medication. In the present study, we evaluated the effects of trace amine compounds, including octopamine, tyramine, 3-methoxytyramine, and synephrine, on SH-SY5Y neuroblastoma cells. Previously, these compounds exhibited TAAR1-specific activity at nanomolar concentrations. However, in SH-SY5Y neuroblastoma cells, the effect of octopamine and 3-methoxytyramine was identified in concentrations of 1000 µM or above and is apparently non-specific. Neither public transcriptomic datasets nor qPCR analysis detected significant TAAR1 expression in SH-SY5Y cells, suggesting that the observed effects may be mediated by adrenoceptors. Among these, ADRA2C was the most highly expressed in SH-SY5Y cells. Analysis of transcriptomic data from the GEO database revealed that adrenoceptors are widely expressed in neuroblastomas. The expression profiles of adrenoceptors in tumors are polymorphic and more complex than in SH-SY5Y cells. Thus, the effects of trace amines on other neuroblastoma cell lines and in vivo tumors warrant further investigation, and the involvement of adrenoceptors in this process may be speculated. Our findings suggest the non-specific activity of trace amines against tumor cells, with a paradoxical stimulatory effect in differentiated neuroblastoma cells, which highlights the need for caution in studies involving TAAR1-specific compounds.