title: Coffee inhibits nuclear factor-kappa B in prostate cancer cells and xenografts.
abstract: Chronic inflammation contributes to prostate cancer and the transcription factor Nuclear Factor-kappa B (NF-κB) is constitutively active in most such cancers. We examine the effects of coffee on NF-κB and on the regulation of selected genes in human-derived prostate cancer cells (PC3) and in PC3 xenografts in athymic nude mice. PC3 cells stably transduced with an NF-κB-luciferase reporter were used both in vitro and for xenografts. NF-κB activity was measured by reporter assays, DNA binding and in vivo imaging. Gene expression was measured in PC3 cells, xenografts and tumor microenvironment by low-density arrays. Western blotting of activated caspases was used to quantify apoptosis. Coffee inhibited TNFα-induced NF-κB activity and DNA-binding in PC3 cells. Furthermore, coffee increased apoptosis and modulated expression of a number of inflammation- and cancer-related genes in TNFα-treated PC3 cells. In vivo imaging revealed a 31% lower NF-κB-luciferase activation in the xenografts of the mice receiving 5% coffee compared to control mice. Interestingly, we observed major changes in gene expression in the PC3 cells in xenografts as compared to PC3 cells in vitro. In PC3 xenografts, genes related to inflammation, apoptosis and cytoprotection were down-regulated in mice receiving coffee, and coffee also affected the gene expression in the xenograft microenvironment. Our data demonstrate that coffee inhibits NF-κB activity in PC3 cells in vitro and in xenografts. Furthermore, coffee modulates transcription of genes related to prostate cancer and inflammation. Our results are the first to suggest mechanistic links between coffee consumption and prostate cancer in an experimental mouse model.
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway. Electronic address: marit.kolberg@medisin.uio.no.
authors.forename: Marit
authors.initials: M
authors.lastname: Kolberg
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway. Electronic address: sigrpe@ous-hf.no.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Pedersen
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway. Electronic address: mikmitake@gmail.com.
authors.forename: Maiko
authors.initials: M
authors.lastname: Mitake
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway. Electronic address: k.l.holm@medisin.uio.no.
authors.forename: Kristine Lillebø
authors.initials: KL
authors.lastname: Holm
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway. Electronic address: s.k.bohn@medisin.uio.no.
authors.forename: Siv Kjølsrud
authors.initials: SK
authors.lastname: Bøhn
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway. Electronic address: h.k.blomhoff@medisin.uio.no.
authors.forename: Heidi Kiil
authors.initials: HK
authors.lastname: Blomhoff
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway; Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway. Electronic address: harald.carlsen@nmbu.no.
authors.forename: Harald
authors.initials: H
authors.lastname: Carlsen
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway; Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway. Electronic address: rune.blomhoff@medisin.uio.no.
authors.forename: Rune
authors.initials: R
authors.lastname: Blomhoff
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1046, 0317 Oslo, Norway. Electronic address: ingvild.paur@medisin.uio.no.
authors.forename: Ingvild
authors.initials: I
authors.lastname: Paur
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003069:Coffee; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D003069:Coffee; D016328:NF-kappa B
keywords: Coffee; In vivo imaging; Microenvironment; NF-κB; Prostate cancer; Xenograft