title: Capsaicin as an inducer of damage-associated molecular patterns (DAMPs) of immunogenic cell death (ICD) in human bladder cancer cells.
abstract: Few conventional cytotoxic anticancer therapeutics induce immunogenic cell death (ICD). This means that they induce tumor cells to undergo apoptosis while eliciting the emission of a spatiotemporal-defined combination of damage-associated molecular patterns (DAMPs) decoded by the immune system to activate antitumor immunity effective for long-term therapeutic success. The neurotoxin capsaicin (CPS) can induce both cancer cell apoptosis and immune-mediated tumor regression. In the present study, we investigated whether CPS is capable of eliciting the emission of ICD hallmarks in human bladder cancer cell lines undergoing apoptosis. We demonstrated that CPS induces pre- and early apoptotic cell surface exposure of calreticulin (CRT), HSP90, and HSP70 as well as ATP release. Moreover, CRT exposure was prevented by inhibition of endoplasmic reticulum-Golgi traffic by brefeldin A. Furthermore, high-mobility group box 1, HSP90, and HSP70 were passively released at late apoptotic stages. We provide the first evidence that CPS is an inducer of ICD hallmarks, suggesting CPS as a novel potential immunogenic cytotoxic agent.
authors.affiliation: Department of Ecological and Biological Sciences (DEB), University of La Tuscia, Largo dell'Università, Blocco C, 01100, Viterbo, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: D'Eliseo
authors.forename: Laura
authors.initials: L
authors.lastname: Manzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Velotti
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D020126:Brefeldin A / Q000037:antagonists & inhibitors / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D002211:Capsaicin / Q000633:toxicity*; D045744:Cell Line, Tumor; D024243:HMGB1 Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D037282:Calreticulin; D024243:HMGB1 Protein; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D020126:Brefeldin A; D000255:Adenosine Triphosphate; D002211:Capsaicin