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Published on: January 29, 2015
An Exploratory Study of High-Concentration Trace Amine Effects and Adrenoceptor Expression Patterns in SH-SY5Y Cells
Aleksandr V Lopachev1, Rogneda B Kazanskaya1, Raul R Gainetdinov1
1Institute of Translational Biomedicine, St. Petersburg State University, Universitetskaya Embankment. 7/9, 199034 St. Petersburg, Russia.
Abstract:
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.
Insights
Trace amine compounds show non-specific activity against neuroblastoma cells, potentially acting via adrenoceptors rather than TAAR1. Caution is advised when using these compounds in cancer research.
Area of Science:
- Pharmacology
- Neuroscience
- Oncology
Background:
- Monoamine receptor ligands are explored for cancer treatment.
- Trace amines like octopamine and tyramine previously showed TAAR1-specific activity.
Purpose of the Study:
- Evaluate trace amine effects on SH-SY5Y neuroblastoma cells.
- Investigate the mechanism of action, specifically TAAR1 vs. adrenoceptors.
Main Methods:
- Cell-based assays on SH-SY5Y neuroblastoma cells.
- Transcriptomic analysis (public datasets and qPCR) for TAAR1 expression.
- Analysis of GEO database for adrenoceptor expression in neuroblastomas.
Main Results:
- Trace amines required high concentrations (≥1000 µM) for effects in SH-SY5Y cells, indicating non-specific activity.
- Significant TAAR1 expression was not detected in SH-SY5Y cells.
- Adrenoceptors, particularly ADRA2C, were highly expressed in SH-SY5Y cells and broadly in neuroblastomas.
- Adrenoceptor expression in tumors is complex and polymorphic.
Conclusions:
- Observed trace amine effects on SH-SY5Y cells are likely adrenoceptor-mediated, not TAAR1-specific.
- Trace amines may exhibit paradoxical stimulatory effects on differentiated neuroblastoma cells.
- Further research is needed on trace amine effects in other neuroblastoma models and in vivo, considering adrenoceptor involvement.
