Reference - Detail
| RRC ID | 61556 |
|---|---|
| Author | Kashima H, Momose F, Umehara H, Miyoshi N, Ogo N, Muraoka D, Shiku H, Harada N, Asai A. |
| Title | Epirubicin, Identified Using a Novel Luciferase Reporter Assay for Foxp3 Inhibitors, Inhibits Regulatory T Cell Activity. |
| Journal | PLoS One |
| Abstract |
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. |
| Volume | 11(6) |
| Pages | e0156643 |
| Published | 2016-1-1 |
| DOI | 10.1371/journal.pone.0156643 |
| PII | PONE-D-16-09801 |
| PMID | 27284967 |
| PMC | PMC4902191 |
| MeSH | Animals Antineoplastic Agents / isolation & purification* Antineoplastic Agents / pharmacology Cells, Cultured Down-Regulation / drug effects Drug Screening Assays, Antitumor / methods* Epirubicin / isolation & purification* Epirubicin / pharmacology Female Forkhead Transcription Factors / antagonists & inhibitors* Genes, Reporter* HEK293 Cells Humans Luciferases* / genetics Luciferases* / metabolism Lymphocyte Activation / drug effects Mice Mice, Inbred BALB C T-Lymphocytes, Regulatory / drug effects* T-Lymphocytes, Regulatory / immunology |
| IF | 2.74 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293(RCB1637) |