4.5 Article

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

Journal

INVESTIGATIONAL NEW DRUGS
Volume 40, Issue 4, Pages 700-708

Publisher

SPRINGER
DOI: 10.1007/s10637-022-01229-3

Keywords

beta-Thujaplicin; Head and neck squamous cell carcinoma; cancer; HNSCC; Radiosensitization

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This study found that beta-Thujaplicin can enhance the sensitivity of HNSCC cell lines to radiotherapy and inhibit cell clonogenicity and migration.
Background Resistance to radiotherapy is a common cause of treatment failure in advanced head and neck squamous cell carcinoma (HNSCC). beta-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. Methods To investigate the effect of beta-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 beta-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. beta-Thujaplicin further led to S-phase arrest and increased the sub-G1 population. Moreover, combined beta-Thujaplicin and irradiation treatment had a higher anti-migratory effect compared to irradiation alone. Conclusions beta-Thujaplicin acts as a radiosensitizer in HNSCC cell lines. Further evaluation of its use in HNSCC therapy is warranted.

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