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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602957PMC
http://dx.doi.org/10.1007/s00432-023-05269-xDOI Listing

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