The radiosensitizing effect of β-Thujaplicin, a tropolone derivative inducing S-phase cell cycle arrest, in head and neck squamous cell carcinoma-derived cell lines

β-Thujaplicin(一种诱导 S 期细胞周期停滞的托酚酮衍生物)对头颈部鳞状细胞癌衍生细胞系的放射增敏作用

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作者:Markus Haas, Teresa Lenz, Lorenz Kadletz-Wanke, Gregor Heiduschka, Bernhard J Jank

Background

Resistance to radiotherapy is a common cause of treatment failure in advanced head and neck squamous cell carcinoma (HNSCC). ß-Thujaplicin, a natural tropolone derivative, acts as an anti-cancer agent and has recently been shown to radiosensitize non-HNSCC cancer cells. However, no data is currently available on its radiosensitizing potential in HNSCC.

Conclusions

ß-Thujaplicin acts as a radiosensitizer in HNSCC cell lines. Further evaluation of its use in HNSCC therapy is warranted.

Methods

To investigate the effect of ß-Thujaplicin and irradiation in HNSCC cell lines CAL27 and FADU, we performed a cell viability assay, colony forming assay, flow cytometry for cell cycle analysis and a wound healing assay. Drug-irradiation interaction was analyzed using a zero-interaction potency model.

Results

Treatment with ß-Thujaplicin led to a dose-dependent decrease in cell viability and enhanced the effect of irradiation. Clonogenic survival was inhibited with synergistic drug-irradiation interaction. ß-Thujaplicin further led to S-phase arrest and increased the sub-G1 population. Moreover, combined ß-Thujaplicin and irradiation treatment had a higher anti-migratory effect compared to irradiation alone. Conclusions: ß-Thujaplicin acts as a radiosensitizer in HNSCC cell lines. Further evaluation of its use in HNSCC therapy is warranted.

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