title: Capsaicin-mediated apoptosis of human bladder cancer cells activates dendritic cells via CD91.
abstract: OBJECTIVE
  Immunostimulation by anticancer cytotoxic drugs is needed for long-term therapeutic success. Activation of dendritic cells (DCs) is crucial to obtain effective and long-lasting anticancer T-cell mediated immunity. The aim of this study was to explore the effect of capsaicin-mediated cell death of bladder cancer cells on the activation of human monocyte-derived CD1a+ immature DCs.
  
  
  METHODS
  Immature DCs (generated from human peripheral blood-derived CD14+ monocytes cultured with granulocyte-macrophage colony stimulating factor and interleukin-4) were cocultured with capsaicin (CPS)-induced apoptotic bladder cancer cells. DC activation was investigated using immunofluorescence and flow cytometric analysis for key surface molecules. In some experiments, CD91 was silenced in immature DCs.
  
  
  RESULTS
  We found that capsaicin-mediated cancer cell apoptosis upregulates CD86 and CD83 expression on DCs, indicating the induction of DC activation. Moreover, silencing of CD91 (a common receptor for damage-associated molecular patterns, such as calreticulin and heat-shock protein-90/70) in immature DCs led to the inhibition of DC activation.
  
  
  CONCLUSIONS
  Our data show that CPS-mediated cancer cell apoptosis activates DCs via CD91, suggesting CPS as an attractive candidate for cancer therapy.
authors.affiliation: Department of Ecological and Biological Sciences, La Tuscia University, Viterbo, Italy.
authors.forename: Maria Saveria
authors.initials: MS
authors.lastname: Gilardini Montani
authors.affiliation: Department of Ecological and Biological Sciences, La Tuscia University, Viterbo, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: D'Eliseo
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Cirone
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Di Renzo
authors.affiliation: Department of Experimental Medicine, La Sapienza University, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Faggioni
authors.affiliation: Department of Molecular Medicine, La Sapienza University, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.affiliation: Department of Ecological and Biological Sciences, La Tuscia University, Viterbo, Italy. Electronic address: velotti@unitus.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Velotti
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D018949:Antigens, CD1 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology* / Q000627:therapeutic use; D002212:Capsicum / Q000737:chemistry*; D003713:Dendritic Cells / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018949:Antigens, CD1; D000972:Antineoplastic Agents, Phytogenic; C419393:CD1a antigen; C508598:IL4 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010936:Plant Extracts; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002211:Capsaicin
keywords: Apoptosis; Bladder cancer; CD91; Capsaicin; Dendritic cells