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.

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.

• Authors: Scott N Pinchot, Joel T Adler, Yinggang Luo, Jianhua Ju, Wenli Li, Ben Shen, Muthusamy Kunnimalaiyaan, Herbert Chen
• Journal: American journal of surgery (Am J Surg) Vol. 197 Issue 3 Pg. 313-9 (Mar 2009) ISSN: 1879-1883 [Electronic] United States
• PMID: 19245907 (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)