Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells

Cancers

Ivan Monteleone¹  Eleonora Franzè²  Giovanni Monteleone²  Carmine Stolfi²  Federica Laudisi²  DavideDi Fusco²  AntonioDi Grazia²  Angela Ortenzi² 

[1]Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy

[2]Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy

关键词: drug repurposing;    anti-helmintic;    endoplasmic reticulum stress;    calreticulin;    ATP;    HMGB1;   

DOI  :  10.3390/cancers12051314

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown