In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma

J Cancer Res Clin Oncol. 2023 Nov;149(16):14691-14699. doi: 10.1007/s00432-023-05269-x. Epub 2023 Aug 16.

Abstract

Purpose: Gamma-secretase inhibitor MK0752 has shown a high therapeutic potential in different solid malignant tumors. Up to now, its antineoplastic effects were not investigated in head and neck squamous cell carcinoma (HNSCC) and particularly in human-papillomavirus (HPV)-positive tumors.

Methods: We conducted cytotoxic, migration, and clonogenic assays in two HPV-negative HNSCC cell lines (Cal27 and FaDu) and one HPV-positive cell line (SCC154). Furthermore, in order to assess the pro-apoptotic effects of MK0752, a Caspase 3/7 Glo assay was performed.

Results: Our experiments revealed antineoplastic effects of MK0752 in all three cell lines. Strong cytotoxic and antimigratory potential was shown in all cell lines, with strongest effects observed in the HPV-positive cell line. Meanwhile, anticlonogenic effects were only shown in Cal27 and SCC154. Most importantly, MK0752 induced apoptosis solely in HPV-positive SCC154.

Conclusions: Our novel findings indicate a therapeutic potential of MK0752 in HPV-positive HNSCC. Indeed, further investigation is needed for validation of our results and for the assessment of the mechanistic background.

Keywords: HNSCC; HPV; MK0752.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Head and Neck Neoplasms* / drug therapy
  • Humans
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / drug therapy

Substances

  • 3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid
  • Antineoplastic Agents