High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma

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Tuomainen , K , Hyytiäinen , A , Al-Samadi , A , Ianevski , P , Ianevski , A , Potdar , S , Turunen , L , Saarela , J , Kuznetsov , S , Wahbi , W , Risteli , M , Mäkitie , A , Monni , O & Salo , T 2021 , ' High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma ' , Scientific Reports , vol. 11 , 14755 . https://doi.org/10.1038/s41598-021-94259-5

Title: High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma
Author: Tuomainen, Katja; Hyytiäinen, Aini; Al-Samadi, Ahmed; Ianevski, Philipp; Ianevski, Aleksandr; Potdar, Swapnil; Turunen, Laura; Saarela, Jani; Kuznetsov, Sergey; Wahbi, Wafa; Risteli, Maija; Mäkitie, Antti; Monni, Outi; Salo, Tuula
Contributor organization: Department of Oral and Maxillofacial Diseases
HUS Head and Neck Center
Medicum
Institute for Molecular Medicine Finland
Computational Systems Medicine
Biosciences
Department of Ophthalmology and Otorhinolaryngology
Clinicum
Department of Oncology
HUSLAB
Date: 2021-07-20
Language: eng
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-021-94259-5
URI: http://hdl.handle.net/10138/334783
Abstract: Conventional chemotherapeutic agents are nonselective, often resulting in severe side effects and the development of resistance. Therefore, new molecular-targeted therapies are urgently needed to be integrated into existing treatment regimens. Here, we performed a high-throughput compound screen to identify a synergistic interaction between ionizing radiation and 396 anticancer compounds. The assay was run using five human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) cell lines cultured on the human tumor-derived matrix Myogel. Our screen identified several compounds with strong synergistic and antagonistic effects, which we further investigated using multiple irradiation doses. Navitoclax, which emerged as the most promising radiosensitizer, exhibited synergy with irradiation regardless of the p53 mutation status in all 13 HNSCC cell lines. We performed a live cell apoptosis assay for two representative HNSCC cell lines to examine the effects of navitoclax and irradiation. As a single agent, navitoclax reduced proliferation and induced apoptosis in a dose-dependent manner, whereas the navitoclax-irradiation combination arrested cell cycle progression and resulted in substantially elevated apoptosis. Overall, we demonstrated that combining navitoclax with irradiation resulted in synergistic in vitro antitumor effects in HNSCC cell lines, possibly indicating the therapeutic potential for HNSCC patients.
Subject: CANCER
COMBINATION
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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