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Krebshemmende Wirkung des ätherischen Salbei-Öls auf eine Plattenepithelzellkarzinom-Zelllinie der Mundhöhle (UMSCC1)

Anticancer activity of Salvia officinalis essential oil against HNSCC cell line (UMSCC1)

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Zusammenfassung

Hintergrund

Das Mundhöhlenkarzinom ist mit mehreren Hunderttausend Neuerkrankungen im Jahr ein weltweites Problem. Die Behandlung ist mit schwierigen Operationen, schweren Nebenwirkungen der medikamentösen Behandlung und allgemein schlechter Prognose verbunden. Da sich die Mehrzahl der heute verwendeten Krebsmedikamente von Wirkstoffen natürlichen Ursprungs ableitet, stellen Naturprodukte noch immer wertvolle Quellen für neue Therapieoptionen. In dieser Untersuchung wurde die zytotoxische Wirkung des ätherischen Öls von Salvia officinalis L. (Salbei) untersucht.

Material und Methoden

Nach wässriger Extraktion aus den Pflanzenteilen wurde das ätherische Öl von Salvia officinalis im Gaschromatographen analysiert. Die Zytotoxizität des ätherischen Öls auf die Plattenepithelzellkarzinom-Zelllinie UMSCC1 wurde im XTT-Assay untersucht. Mit der daraus ermittelten halbmaximalen inhibitorischen Konzentration (IC50) des ätherischen Öls wurde eine microarraybasierte Analyse der Genexpression durchgeführt. Die Werte der differenziellen Genaktivitäten wurden anschließend aktivierten Signalwegen zugeordnet.

Ergebnisse

Das ätherische Öl von Salvia officinalis enthielt vor allem die Monoterpene Thujon, β-Pinen und 1,8-Cineol. Niedrige Konzentrationen erhöhten im XTT-Assay die Vitalität der UMSCC1 bis zu einem Schwellenwert um die IC50 von 135 µg/ml, ab dem die Vitalität rasch gegen Null ging. Die differenzielle Genaktivität in der Microarray-Analyse ergab vor allem Gene aus den Bereichen Krebs, Zellwachstum und -proliferation, Zelltod, Zellmorphologie, Zellzyklus und DNA-Reparatur. Die am deutlichsten aktivierten Signalwege waren der Aryl-Hydrocarbon-Rezeptor-Signalweg, der Zellzyklusübergang von der G1- zur S-Phase und der p53-Signalweg.

Schlussfolgerung

Diese Untersuchung belegt zum ersten Mal die zytotoxische Wirkung des ätherischen Öls von Salvia officinalis auf eine humane Plattenepithelzellkarzinom-Zelllinie (UMSCC1) der Mundhöhle. Das therapeutische Potenzial des Salbeis reicht damit möglicherweise weit über die tradierten Anwendungsgebiete in der Hals-Nasen-Ohren-Heilkunde hinaus.

Abstract

Background

Every year there are several hundred thousand new cases of oral cancer worldwide. Clinical oncology is still challenged by toxicity and side effects of multimodal therapy strategies in which is associated with poor prognosis for patients. There is an urgent necessity to develop novel therapy strategies. As the majority of anticancer drugs are of natural origin, natural products represent a valuable source for the identification and development of novel treatment options for cancer. The aim of this investigation was to study the cytotoxicity of Salvia officinalis L. (sage) essential oil.

Methods

Salvia officinalis essential oil was gained by aqueous extraction from plant material and subsequently analyzed by gas chromatography. The cytotoxicity of the essential oil on the squamous human cell carcinoma cell line of the oral cavity (UMSCC1) was assessed with the XTT assay. These experiments revealed the half maximal inhibitory concentration (IC50) of the essential oil. It was used in the microarray-based analysis of gene expression of UMSSC1 cells. The results were submitted to a signaling pathway analysis.

Results

The main constituents of Salvia officinalis essential oil include the monoterpenes thujone, β-pinene, and 1,8-cineol. Low concentrations of the essential oil increased vitality of the UMSCC1 cells. Beyond the concentration of the IC50 of 135 µg/ml, sage essential oil reduced UMSSC1 cells viability to a minimum. In the microarray gene expression analysis, genes involved in cancer, cellular growth and proliferation, cell death, cell morphology, cell cycle, gene expression, and DNA repair were the most prominent. The three most significantly regulated pathways by sage were aryl hydrocarbon receptor signaling, cell cycle (G1/S checkpoint) regulation, and p53 signaling.

Conclusion

To the best of our knowledge, this study suggests for the first time the ability of Salvia officinalis essential oil to inhibit human HNSCC cell growth. The therapeutic potential of sage essential oil might exceed that of its common use in otorhinolaryngology.

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Authors and Affiliations

  1. Hals-, Nasen- und Ohrenklinik, Universität Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland

    S. Sertel & P.K. Plinkert

  2. Pharmazeutische Biologie (C015), Deutsches Krebsforschungszentrum, Heidelberg, Deutschland

    S. Sertel & T. Eichhorn

  3. AK Pharmazeutische Biologie, Institut für Pharmazie und Biochemie, Universität Mainz, Mainz, Deutschland

    S. Sertel, T. Eichhorn & T. Efferth

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  1. S. Sertel
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  2. T. Eichhorn
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Correspondence to S. Sertel.

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Sertel, S., Eichhorn, T., Plinkert, P. et al. Krebshemmende Wirkung des ätherischen Salbei-Öls auf eine Plattenepithelzellkarzinom-Zelllinie der Mundhöhle (UMSCC1). HNO 59, 1203–1208 (2011). https://doi.org/10.1007/s00106-011-2274-3

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