title: Effects of adipocyte-secreted factors on cell cycle progression in HT29 cells.
abstract: BACKGROUND
  Obesity is a chronic sub-inflammatory condition which is a risk factor for several cancer diseases, e.g. colon cancer. Adipose tissue secretes biologically active factors like leptin with a known pro-inflammatory or mitogenic activity. Both, chronic inflammation and an increased cell proliferation are considered to play an important role in colon carcinogenesis. Diverse phytochemicals were shown to have cell growth inhibiting effects.
  
  
  OBJECTIVE
  The aim was to investigate whether adipocytes could mediate a proliferative capacity to HT29, a human colon adenocarcinoma cell line, and whether phytochemicals could modulate this effect.
  
  
  METHODS
  Infranatants of adipocyte cultures from different donors were prepared and the effects of those conditioned adipocyte media (CAM) on HT29 cell growth were measured. Additionally, cell cycle progression was analyzed by flow cytometry after CAM treatment and ERK 1/2 phosphorylation was analyzed.
  
  
  RESULTS
  CAM from a subgroup of adipose tissue donors stimulated HT29 cell growth, whereas others did not. This effect seems to be mediated via the ERK 1/2 pathway. Furthermore, CAM caused changes in cell cycle distribution with a shift of HT29 cells from G1- into the S-phase. This effect could be mimicked by leptin (1 nM). Co-incubation of CAM-treated HT29 cultures with beta-carotene or EGCG did not have a significant impact on cell cycle progression, whereas genistein (30 microM) tended to inhibit the CAM-stimulated transition of cells into the S-phase.
  
  
  CONCLUSIONS
  This study confirmed the mitogenic activity of leptin in HT29 cells, although leptin secretion from adipocytes is not likely to be responsible for CAM-stimulated cell growth in our test system. The investigated phytochemicals seem to have only a minor influence on CAM-mediated cell cycle progression.
authors.affiliation: Chair of the Biofunctionality of Food, Dept. of Food and Nutrition, Technische Universität München, Freising, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schnäbele
authors.forename: Silvia
authors.initials: S
authors.lastname: Roser
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rechkemmer
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.forename: Thomas
authors.initials: T
authors.lastname: Skurk
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism / Q000494:pharmacology; D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D019207:beta Carotene / Q000494:pharmacology
chemical_list: D054392:Adipokines; D052242:Adiponectin; D017077:Culture Media, Conditioned; D020738:Leptin; D019207:beta Carotene; D019833:Genistein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3