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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dc.contributor.author Tuomainen, Katja
dc.contributor.author Hyytiäinen, Aini
dc.contributor.author Al-Samadi, Ahmed
dc.contributor.author Ianevski, Philipp
dc.contributor.author Ianevski, Aleksandr
dc.contributor.author Potdar, Swapnil
dc.contributor.author Turunen, Laura
dc.contributor.author Saarela, Jani
dc.contributor.author Kuznetsov, Sergey
dc.contributor.author Wahbi, Wafa
dc.contributor.author Risteli, Maija
dc.contributor.author Mäkitie, Antti
dc.contributor.author Monni, Outi
dc.contributor.author Salo, Tuula
dc.date.accessioned 2021-09-30T12:46:01Z
dc.date.available 2021-09-30T12:46:01Z
dc.date.issued 2021-07-20
dc.identifier.citation 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
dc.identifier.other PURE: 168692219
dc.identifier.other PURE UUID: 5aabd5f3-a0a5-4138-9106-951888db25de
dc.identifier.other WOS: 000692201200015
dc.identifier.other ORCID: /0000-0001-6039-0088/work/100825237
dc.identifier.other ORCID: /0000-0001-7306-7175/work/100825354
dc.identifier.other ORCID: /0000-0002-7780-482X/work/100827014
dc.identifier.other ORCID: /0000-0003-3330-1670/work/100827137
dc.identifier.other ORCID: /0000-0002-2778-6918/work/100827433
dc.identifier.uri http://hdl.handle.net/10138/334783
dc.description.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. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject CANCER
dc.subject COMBINATION
dc.subject 3122 Cancers
dc.title High-throughput compound screening identifies navitoclax combined with irradiation as a candidate therapy for HPV-negative head and neck squamous cell carcinoma en
dc.type Article
dc.contributor.organization Department of Oral and Maxillofacial Diseases
dc.contributor.organization HUS Head and Neck Center
dc.contributor.organization Medicum
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Computational Systems Medicine
dc.contributor.organization Biosciences
dc.contributor.organization Department of Ophthalmology and Otorhinolaryngology
dc.contributor.organization Clinicum
dc.contributor.organization Department of Oncology
dc.contributor.organization HUSLAB
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41598-021-94259-5
dc.relation.issn 2045-2322
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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