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

التفاصيل البيبلوغرافية
العنوان: High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma
المؤلفون: Katja Tuomainen, Aini Hyytiäinen, Ahmed Al-Samadi, Philipp Ianevski, Aleksandr Ianevski, Swapnil Potdar, Laura Turunen, Jani Saarela, Sergey Kuznetsov, Wafa Wahbi, Maija Risteli, Antti Mäkitie, Outi Monni, Tuula Salo
المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
بيانات النشر: Nature Portfolio, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-021-94259-5
URL الوصول: https://doaj.org/article/94f7ab850a6441f089e9e315a0b84667
رقم الأكسشن: edsdoj.94f7ab850a6441f089e9e315a0b84667
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-021-94259-5