Academic Journal
Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity.
| العنوان: | Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity. |
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| المؤلفون: | Hajime Kashima, Fumiyasu Momose, Hiroshi Umehara, Nao Miyoshi, Naohisa Ogo, Daisuke Muraoka, Hiroshi Shiku, Naozumi Harada, Akira Asai |
| المصدر: | PLoS ONE, Vol 11, Iss 6, p e0156643 (2016) |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Forkhead box protein p3 (Foxp3) is crucial to the development and suppressor function of regulatory T cells (Tregs) that have a significant role in tumor-associated immune suppression. Development of small molecule inhibitors of Foxp3 function is therefore considered a promising strategy to enhance anti-tumor immunity. In this study, we developed a novel cell-based assay system in which the NF-κB luciferase reporter signal is suppressed by the co-expressed Foxp3 protein. Using this system, we screened our chemical library consisting of approximately 2,100 compounds and discovered that a cancer chemotherapeutic drug epirubicin restored the Foxp3-inhibited NF-κB activity in a concentration-dependent manner without influencing cell viability. Using immunoprecipitation assay in a Treg-like cell line Karpas-299, we found that epirubicin inhibited the interaction between Foxp3 and p65. In addition, epirubicin inhibited the suppressor function of murine Tregs and thereby improved effector T cell stimulation in vitro. Administration of low dose epirubicin into tumor-bearing mice modulated the function of immune cells at the tumor site and promoted their IFN-γ production without direct cytotoxicity. In summary, we identified the novel action of epirubicin as a Foxp3 inhibitor using a newly established luciferase-based cellular screen. Our work also demonstrated our screen system is useful in accelerating discovery of Foxp3 inhibitors. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC4902191?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0156643 |
| URL الوصول: | https://doaj.org/article/af4abd82df1e4e5bbae3febfaf2d1e8b |
| رقم الانضمام: | edsdoj.f4abd82df1e4e5bbae3febfaf2d1e8b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0156643 |