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

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.

Optimization of a Three-Dimensional Culturing Method for Assessing the Impact of Cisplatin on Notch Signaling in Head and Neck Squamous Cell Carcinoma (HNSCC)

“…Here, we use CRE in combination with cisplatin to test the hypothesis that targeting both DNA damage response and Notch signaling may result in potentially synergistic effects. The functional and molecular relationship between Notch signaling and cisplatin resistance has been only poorly investigated thus far [20][21][22] and almost exclusively in routine two-dimensional monolayer cell cultures.…”