Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells
Colorectal cancer (CRC) is a major cause of cancer-related death in the world. Emerging evidence suggests that the clinical success of conventional chemotherapy does not merely rely on cell toxicity, but also results from the restoration of tumor immune surveillance. Anti-tumor immune response can b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/5/1314 |
| _version_ | 1797567316613922816 |
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| author | Antonio Di Grazia Federica Laudisi Davide Di Fusco Eleonora Franzè Angela Ortenzi Ivan Monteleone Giovanni Monteleone Carmine Stolfi |
| author_facet | Antonio Di Grazia Federica Laudisi Davide Di Fusco Eleonora Franzè Angela Ortenzi Ivan Monteleone Giovanni Monteleone Carmine Stolfi |
| author_sort | Antonio Di Grazia |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is a major cause of cancer-related death in the world. Emerging evidence suggests that the clinical success of conventional chemotherapy does not merely rely on cell toxicity, but also results from the restoration of tumor immune surveillance. Anti-tumor immune response can be primed by immunogenic cell death (ICD), a form of apoptosis associated with endoplasmic reticulum stress (ERS) induction and the expression/release of specific damage-associated molecular patterns (DAMPs). Unfortunately, a limited number of ICD inducers have been identified so far. The anti-helmintic drug rafoxanide has recently showed anti-tumor activity in different cancer types, including CRC. As such latter effects relied on ERS activation, we here investigated whether rafoxanide could promote ICD of CRC cells. The potential of rafoxanide to induce ICD-related DAMPs in both human and mouse CRC cells was assessed by flow-cytometry, chemiluminescent assay and ELISA. In addition, the immunogenic potential of rafoxanide was assessed in vivo using a vaccination assay. Rafoxanide induced all the main DAMPs (ecto-calreticulin exposure, adenosine triphosphate (ATP)/high mobility group box 1 (HMGB1) release) required for ICD. We observed a marked increase of tumor-free survival among immunocompetent mice immunized with rafoxanide-treated dying tumor cells as compared with sham. Altogether, our data indicate rafoxanide as a bona fide ICD inducer. |
| first_indexed | 2024-03-10T19:40:05Z |
| format | Article |
| id | doaj.art-c893c57fa1cf4858a38250ad349de108 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:40:05Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c893c57fa1cf4858a38250ad349de1082023-11-20T01:19:38ZengMDPI AGCancers2072-66942020-05-01125131410.3390/cancers12051314Rafoxanide Induces Immunogenic Death of Colorectal Cancer CellsAntonio Di Grazia0Federica Laudisi1Davide Di Fusco2Eleonora Franzè3Angela Ortenzi4Ivan Monteleone5Giovanni Monteleone6Carmine Stolfi7Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyDepartment of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, ItalyColorectal cancer (CRC) is a major cause of cancer-related death in the world. Emerging evidence suggests that the clinical success of conventional chemotherapy does not merely rely on cell toxicity, but also results from the restoration of tumor immune surveillance. Anti-tumor immune response can be primed by immunogenic cell death (ICD), a form of apoptosis associated with endoplasmic reticulum stress (ERS) induction and the expression/release of specific damage-associated molecular patterns (DAMPs). Unfortunately, a limited number of ICD inducers have been identified so far. The anti-helmintic drug rafoxanide has recently showed anti-tumor activity in different cancer types, including CRC. As such latter effects relied on ERS activation, we here investigated whether rafoxanide could promote ICD of CRC cells. The potential of rafoxanide to induce ICD-related DAMPs in both human and mouse CRC cells was assessed by flow-cytometry, chemiluminescent assay and ELISA. In addition, the immunogenic potential of rafoxanide was assessed in vivo using a vaccination assay. Rafoxanide induced all the main DAMPs (ecto-calreticulin exposure, adenosine triphosphate (ATP)/high mobility group box 1 (HMGB1) release) required for ICD. We observed a marked increase of tumor-free survival among immunocompetent mice immunized with rafoxanide-treated dying tumor cells as compared with sham. Altogether, our data indicate rafoxanide as a bona fide ICD inducer.https://www.mdpi.com/2072-6694/12/5/1314drug repurposinganti-helminticendoplasmic reticulum stresscalreticulinATPHMGB1 |
| spellingShingle | Antonio Di Grazia Federica Laudisi Davide Di Fusco Eleonora Franzè Angela Ortenzi Ivan Monteleone Giovanni Monteleone Carmine Stolfi Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells Cancers drug repurposing anti-helmintic endoplasmic reticulum stress calreticulin ATP HMGB1 |
| title | Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells |
| title_full | Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells |
| title_fullStr | Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells |
| title_full_unstemmed | Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells |
| title_short | Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells |
| title_sort | rafoxanide induces immunogenic death of colorectal cancer cells |
| topic | drug repurposing anti-helmintic endoplasmic reticulum stress calreticulin ATP HMGB1 |
| url | https://www.mdpi.com/2072-6694/12/5/1314 |
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