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
Abstract
AbstractConventional 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.
Funder
Syöpäjärjestöt
Syöpäsäätiö
Doctoral Program in Clinical Research at the University of Helsinki
Emil Aaltosen Säätiö
Doctoral Program of the Faculty of Medicine, University of Helsinki
Jane ja Aatos Erkon Säätiö
Sigrid Juséliuksen Säätiö
The Helsinki University Central Hospital research funds
Publisher
Springer Science and Business Media LLC
Cited by
9 articles.
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