Zerumbone acts as a radiosensitizer in head and neck squamous cell carcinoma

Invest New Drugs. 2022 Apr;40(2):224-231. doi: 10.1007/s10637-021-01190-7. Epub 2021 Oct 6.

Abstract

Introduction: Zerumbone is a phytochemical compound of the ginger plant Zingiber zerumbet with cytotoxic effects in various cancer cell lines. To date, zerumbone has shown an antiproliferative effect in oral squamous cell carcinoma cells lines. However, the effect of combination with radiation or cisplatin in head and neck squamous cell carcinoma (HNSCC) is unclear. The aim of this study was to investigate the effect of zerumbone alone, and in combination with irradiation and cisplatin on HNSCC cell lines.

Methods: The three HNSCC cell lines SCC25, Cal27 and FaDu were treated with zerumbone, radiation and/or cisplatin. Cell viability and clonogenic assays were performed. The interaction between zerumbone and radiation or cisplatin was evaluated using the combination index. Apoptosis was measured by flow cytometry and cell migration was assessed using a wound healing assay.

Results: Treatment with zerumbone resulted in a dose dependent induction of cytotoxicity and apoptosis in all three cell lines. The combination with cisplatin revealed a synergistic to additive effect in Cal27. The clonogenic assay showed a significant radiosensitizing effect in all three cell lines. The wound healing assay showed a reduction of cell migration in Cal27.

Conclusion: The natural compound zerumbone shows a cytotoxic and proapoptotic effect on HNSCC cell lines. Furthermore, zerumbone enhances the radiation effect in all three cell lines and thus may be a suitable candidate for combination therapy in HNSCC.

Keywords: Cytotoxic; Head and neck squamous cell carcinoma; Natural products; Radiation; Zerumbone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / pathology
  • Carcinoma, Squamous Cell* / radiotherapy
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Mouth Neoplasms* / drug therapy
  • Radiation-Sensitizing Agents* / pharmacology
  • Radiation-Sensitizing Agents* / therapeutic use
  • Sesquiterpenes
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / radiotherapy

Substances

  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Sesquiterpenes
  • zerumbone
  • Cisplatin