title: The vanilloid capsaicin induces IL-6 secretion in prostate PC-3 cancer cells.
abstract: Capsaicin (8-methyl-N-vanillyl-6-nonenamide), a constituent of green and red peppers, has been linked with suppression of tumorigenesis through a mechanism that is not well understood. In the present study, we examined the effects of capsaicin on the production of the cytokine interleukin (IL)-6 by PC-3 cells at both protein and mRNA levels which were evaluated by ELISA and real-time PCR, respectively. Capsaicin-treated PC-3 cells increased the synthesis and secretion of IL-6 which was abrogated by the transient receptor potential vanilloid receptor subtype 1 (TRPV1) antagonist capsazepine, as well as by inhibitors of PKC-α, phosphoinositol-3 phosphate kinase (PI-3K), Akt and extracellular signal-regulated protein kinase (ERK). We analyzed the role of capsaicin in the tumor necrosis factor (TNF)-α secretion by PC-3 cells which was increased at shorter times than IL-6 production. Furthermore, incubation of PC-3 cells with an anti-TNF-α antibody blocked the capsaicin-induced IL-6 secretion. These results raise the possibility that capsaicin-mediated IL-6 increase in prostate cancer PC-3 cells is regulated at least in part by TNF-α secretion and signaling pathway involving Akt, ERK and PKC-α activation.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Alcalá, 28871 Alcalá de Henares Madrid, Spain. sophie.malagarie@gmail.com
authors.forename: Sophie
authors.initials: S
authors.lastname: Malagarie-Cazenave
authors.forename: Nuria
authors.initials: N
authors.lastname: Olea-Herrero
authors.forename: Diana
authors.initials: D
authors.lastname: Vara
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morell
authors.forename: Inés
authors.initials: I
authors.lastname: Díaz-Laviada
mesh_terms: D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C071423:capsazepine; D002211:Capsaicin