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Published on: April 22, 2019
In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma
Sara Varatanovic1, Stefan Stoiber2,3, Markus Haas1
1Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
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.
Insights
The gamma-secretase inhibitor MK0752 demonstrates significant antineoplastic effects in head and neck squamous cell carcinoma (HNSCC) cell lines. Notably, MK0752 shows enhanced efficacy and induces apoptosis specifically in human papillomavirus (HPV)-positive HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Gamma-secretase inhibitor MK0752 exhibits therapeutic potential in various solid tumors.
- Antineoplastic effects of MK0752 have not been previously studied in head and neck squamous cell carcinoma (HNSCC), especially in human papillomavirus (HPV)-positive subtypes.
Purpose of the Study:
- To investigate the antineoplastic effects of gamma-secretase inhibitor MK0752 in HNSCC.
- To determine the efficacy of MK0752 in both HPV-negative and HPV-positive HNSCC cell lines.
- To assess the pro-apoptotic potential of MK0752 in HNSCC.
Main Methods:
- Cytotoxic, migration, and clonogenic assays were performed on two HPV-negative (Cal27, FaDu) and one HPV-positive (SCC154) HNSCC cell lines.
- Caspase 3/7 Glo assay was utilized to evaluate the pro-apoptotic effects of MK0752.
- Comparative analysis of MK0752's effects across different HNSCC subtypes.
Main Results:
- MK0752 demonstrated antineoplastic effects in all tested HNSCC cell lines.
- Strong cytotoxic and antimigratory activities were observed, with the most significant effects in the HPV-positive cell line.
- MK0752 induced apoptosis exclusively in the HPV-positive SCC154 cell line, while anticlonogenic effects were observed in Cal27 and SCC154.
Conclusions:
- MK0752 shows promising therapeutic potential for HPV-positive HNSCC.
- Further research is warranted to validate these findings and elucidate the underlying mechanistic pathways.
- The study highlights the differential sensitivity of HNSCC subtypes to gamma-secretase inhibition.
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