title: Immune suppressive effect of cinnamaldehyde due to inhibition of proliferation and induction of apoptosis in immune cells: implications in cancer.
abstract: BACKGROUND
  Besides its anti-inflammatory effects, cinnamaldehyde has been reported to have anti-carcinogenic activity. Here, we investigated its impact on immune cells.
  
  
  METHODS
  Activation of nuclear factor-κB by cinnamaldehyde (0-10 µg/ml) alone or in combination with lipopolysaccharide was assessed in THP1XBlue human monocytic cell line and in human peripheral blood mononuclear cells (PBMCs). Proliferation and secretion of cytokines (IL10 and TNFα) was determined in primary immune cells and the human cell lines (THP1, Jurkat E6-1 and Raji cell lines) stimulated with cinnamaldehyde alone or in conjunction with lipopolysaccharide. Nitric oxide was determined in mouse RAW264.7 cells. Moreover, different treated PBMCs were stained for CD3, CD20 and AnnexinV.
  
  
  RESULTS
  Low concentrations (up to 1 µg/ml) of cinnamaldehyde resulted in a slight increase in nuclar factor-kB activation, whereas higher concentrations led to a dose-dependent decrease of nuclear factor-kB activation (up to 50%) in lipopolysachharide-stimulated THP1 cells and PBMCs. Accordingly, nitric oxide, interleukin 10 secretion as well as cell proliferation were reduced in lipopolysachharide-stimulated RAW264.7 cells, PBMCs and THP1, Raji and Jurkat-E6 immune cells in the presence of cinnamaldehyde in a concentration-dependent manner. Flow cytometric analysis of PBMCs revealed that CD3+ were more affected than CD20+ cells to apopotosis by cinnamaldehyde.
  
  
  CONCLUSIONS
  We attribute the anti-inflammatory properties of cinnamaldehyde to its ability to block nuclear factor-κB activation in immune cells. Treatment with cinnamaldehyde led to inhibition of cell viability, proliferation and induced apoptosis in a dose-dependent manner in primary and immortalized immune cells. Therefore, despite its described anti-carcinogenic property, treatment with cinnamaldehyde in cancer patients might be contraindicated due to its ability to inhibit immune cell activation.
authors.affiliation: Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna and University of Vienna, Vienna, Austria.
authors.forename: Franziska
authors.initials: F
authors.lastname: Roth-Walter
authors.affiliation: Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna and University of Vienna, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Moskovskich
authors.affiliation: Biotechnology Department, Center for Plant Biotechnology and Genomics, Technical University Madrid, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gomez-Casado
authors.affiliation: Biotechnology Department, Center for Plant Biotechnology and Genomics, Technical University Madrid, Madrid, Spain.
authors.forename: Araceli
authors.initials: A
authors.lastname: Diaz-Perales
authors.affiliation: Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna and University of Vienna, Vienna, Austria; Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Oida
authors.affiliation: Comparative Immunology and Oncology, Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Singer
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna, Vienna, Austria.
authors.forename: Tamar
authors.initials: T
authors.lastname: Kinaciyan
authors.affiliation: Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria.
authors.forename: Heidemarie C
authors.initials: HC
authors.lastname: Fuchs
authors.affiliation: Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University of Vienna and University of Vienna, Vienna, Austria; Comparative Immunology and Oncology, Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D000171:Acrolein; C012843:cinnamaldehyde