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Updated: Apr 19, 2026

Live-cell Measurement of Odorant Receptor Activation Using a Real-time cAMP Assay
Published on: October 2, 2017
Monoterpene (-)-citronellal affects hepatocarcinoma cell signaling via an olfactory receptor
Désirée Maßberg1, Annika Simon1, Dieter Häussinger2
1Department of Cell Physiology, Ruhr-University Bochum, 44801 Bochum, Germany.
Abstract:
Terpenes are the major constituents of essential oils in plants. In recent years, terpenes have become of clinical relevance due to their ability to suppress cancer development. Their effect on cellular proliferation has made them promising agents in the prevention or treatment of many types of cancer. In the present study, a subset of different monoterpenes was investigated for their molecular effects on the hepatocellular carcinoma cell line Huh7. Using fluorometric calcium imaging, acyclic monoterpene (-)-citronellal was found to induce transient Ca(2+) signals in Huh7 cells by activating a cAMP-dependent signaling pathway. Moreover, we detected the (-)-citronellal-activated human olfactory receptor OR1A2 at the mRNA and protein levels and demonstrated its potential involvement in (-)-citronellal-induced calcium signaling in Huh7 cells. Furthermore, activation of OR1A2 results in phosphorylation of p38 MAPK and reduced cell proliferation, indicating an effect on hepatocellular carcinoma progression. Here, we provide for the first time data on the molecular mechanism evoked by (-)-citronellal in human hepatocellular carcinoma cells. The identified olfactory receptor could serve as a potential therapeutic target for cancer diagnosis and treatment.
Insights
(-)-Citronellal, a plant terpene, activates olfactory receptor OR1A2 in liver cancer cells. This molecular pathway reduces cancer cell proliferation, offering a potential therapeutic target for hepatocellular carcinoma.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Terpenes, found in essential oils, are gaining clinical importance for their cancer-suppressing properties.
- Their impact on cellular proliferation suggests potential in cancer prevention and treatment.
Purpose of the Study:
- To investigate the molecular effects of monoterpenes on the hepatocellular carcinoma cell line Huh7.
- To elucidate the mechanism of action of (-)-citronellal in liver cancer cells.
Main Methods:
- Fluorometric calcium imaging to detect intracellular calcium signals.
- mRNA and protein analysis to identify olfactory receptor expression.
- Western blotting to assess MAPK pathway activation.
Main Results:
- (-)-Citronellal induced transient calcium signals in Huh7 cells via a cAMP-dependent pathway.
- The human olfactory receptor OR1A2 was identified and implicated in (-)-citronellal signaling.
- OR1A2 activation led to p38 MAPK phosphorylation and reduced hepatocellular carcinoma cell proliferation.
Conclusions:
- (-)-Citronellal exerts molecular effects on human hepatocellular carcinoma cells through OR1A2 activation.
- This pathway influences cancer progression by reducing cell proliferation.
- The identified olfactory receptor OR1A2 presents a potential therapeutic target for liver cancer diagnosis and treatment.
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