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Tautomycin suppresses growth and neuroendocrine hormone markers in carcinoid cells through activation of the Raf-1 pathway.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsScott N Pinchot, Joel T Adler, Yinggang Luo, Jianhua Ju, Wenli Li, Ben Shen, Muthusamy Kunnimalaiyaan, Herbert Chen
JournalAmerican journal of surgery (Am J Surg) Vol. 197 Issue 3 Pg. 313-9 (Mar 2009) ISSN: 1879-1883 [Electronic] United States
PMID19245907 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Pyrans
  • Spiro Compounds
  • tautomycin
  • Proto-Oncogene Proteins c-raf
Topics
  • Biomarkers, Tumor (metabolism)
  • Carcinoid Tumor
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Humans
  • Neurosecretory Systems (drug effects)
  • Proto-Oncogene Proteins c-raf (metabolism)
  • Pyrans (pharmacology)
  • Signal Transduction (drug effects)
  • Spiro Compounds (pharmacology)

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