Abstract
Background and Purpose:
Betulinic acid, a pentacyclic triterpene, is a new cytotoxic compound active on melanoma, neuroblastoma, glioblastoma and head and neck squamous cell carcinoma (HNSCC) cells. In combination with irradiation it has been shown to have an additive effect on growth inhibition in melanoma cells. In this study, the radiosensitizing effect of betulinic acid on sequential irradiation was investigated in HNSCC cell lines.
Material and Methods:
Two HNSCC cell lines, SCC9 and SCC25, were treated with increasing doses of betulinic acid and sequentially irradiated with a single boost of 4 Gy from a conventional radiation source. The cells were counted, the surviving fraction was determined, and colony-forming assays were performed.
Results:
It could be shown that betulinic acid alone inhibits cell survival, affects cell survival additively in combination with irradiation and decreases clonogenic survival in both cell lines when applied alone.
Conclusion:
Betulinic acid could be a promising treatment agent in radioresistant head and neck cancer. A combination of betulinic acid with radiotherapy seems to be beneficial.
Zusammenfassung
Hintergrund und Ziel:
Betulinsäure, ein pentazyklisches Triterpenoid, ist ein neuer zytotoxischer Wirkstoff mit Wirkung gegen Melanom-, Neuroblastom-, Glioblastom- sowie Kopf- und Halstumorzellen. In Kombination mit Radiotherapie zeigte sich ein additiver Effekt auf die Wachstumshemmung in Melanomzellen. In dieser Studie wurde untersucht, ob Betulinsäure ein Radiosensitizer bei sequentieller Bestrahlung von Kopf- und Halstumorzellen ist.
Material und Methodik:
Die beiden Kopf- und Halstumorzelllinien SCC9 und SCC25 wurden mit ansteigenden Dosen von Betulinsäure und sequentieller Radiotherapie mit einer Einzeldosis von 4 Gy (Abbildungen 1a und 1b) an einem konventionellen Bestrahlungsgerät behandelt. Dann wurden die Zellen gezählt, das Überleben bestimmt (Abbildungen 2a und 2b) und Koloniebildungsassays durchgeführt (Abbildungen 3a und 3b). Die immunhistochemische Untersuchung erfolgte mit dem M30-Antikörper zur Visualisierung der Apoptose (Abbildungen 4a und 4b).
Ergebnisse:
Es konnte gezeigt werden, dass Betulinsäure allein das Zellüberleben inhibiert, additiv in Kombination mit Radiotherapie agiert und in beiden Zelllinien die Koloniebildungsfähigkeit herabsetzt.
Schlussfolgerung:
Betulinsäure könnte ein vielversprechendes Chemotherapeutikum bei radiotherapieresistenten Kopf- und Halstumoren sein. Eine Kombination von Betulinsäure und Strahlentherapie scheint vorteilhaft.
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Eder-Czembirek, C., Erovic, B.M., Czembirek, C. et al. Betulinic Acid a Radiosensitizer in Head and Neck Squamous Cell Carcinoma Cell Lines. Strahlenther Onkol 186, 143–148 (2010). https://doi.org/10.1007/s00066-010-2069-6
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DOI: https://doi.org/10.1007/s00066-010-2069-6