title: Tautomycin suppresses growth and neuroendocrine hormone markers in carcinoid cells through activation of the Raf-1 pathway.
abstract: BACKGROUND
  Carcinoids are neuroendocrine (NE) tumors with limited treatment options. Raf-1 pathway activation has been shown to suppress hormone production in carcinoid cells. We investigated a novel treatment for carcinoid cell growth based on pharmacologic Raf-1 activation using the compound tautomycin (TTY).
  
  
  METHODS
  Human carcinoid cells were treated with TTY for 48 hours. Western blot analysis was used to demonstrate Raf-1 pathway activation by phosphorylation of ERK1/2 and to determine the effect on NE tumor markers. Cellular growth was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay.
  
  
  RESULTS
  Treatment with TTY resulted in dose-dependent activation of the Raf-1 pathway. Furthermore, a significant decrease in NE tumor markers was seen. Importantly, TTY inhibited carcinoid cellular growth and induced the cell-cycle inhibitors p21 and p27.
  
  
  CONCLUSIONS
  TTY activates the Raf-1 pathway, limits carcinoid cell growth, and suppresses NE marker production in vitro. This new compound warrants further investigation in animal models of carcinoid cancer.
authors.affiliation: Endocrine Surgery Research Laboratories, Department of Surgery, University of Wisconsin, Madison, WI, USA.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Pinchot
authors.forename: Joel T
authors.initials: JT
authors.lastname: Adler
authors.forename: Yinggang
authors.initials: Y
authors.lastname: Luo
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ju
authors.forename: Wenli
authors.initials: W
authors.lastname: Li
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Kunnimalaiyaan
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002276:Carcinoid Tumor; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009490:Neurosecretory Systems / Q000187:drug effects*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D011714:Pyrans / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D011714:Pyrans; D013141:Spiro Compounds; C053079:tautomycin; D019908:Proto-Oncogene Proteins c-raf