Xanthohumol inhibits the neuroendocrine transcription factor achaete-scute complex-like 1, suppresses proliferation, and induces phosphorylated ERK1/2 in medullary thyroid cancer

Am J Surg. 2010 Mar;199(3):315-8; discussion 318. doi: 10.1016/j.amjsurg.2009.08.034.

Abstract

Background: Achaete-scute complex-like 1 (ASCL1) is a transcription factor important in the malignant development of medullary thyroid cancer (MTC). Activation of Raf-1 signaling is associated with ASCL1 suppression and growth inhibition. Xanthohumol, a natural compound, has recently been shown to have anticancer properties. We thus hypothesized that xanthohumol would suppress growth by activating Raf-1 signaling, thus altering the malignant phenotype of MTC.

Methods: Human MTC cells were treated with xanthohumol (0-30 micromol/L) for up to 6 days. Proliferation was measured by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) colorimetric assay. Western blot analysis was performed for ASCL1 and markers of Raf-1 pathway activation.

Results: Treatment of MTC cells with xanthohumol resulted in a dose dependent inhibition of growth. Additionally, induction of phosphorylated ERK1/2 and a reduction of ASCL1 protein was noted.

Conclusions: Xanthohumol is a potent Raf-1 activator in MTC cells. This compound suppresses MTC growth, alters the malignant phenotype, and warrants further preclinical study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Drug Screening Assays, Antitumor
  • Flavonoids / pharmacology*
  • Humans
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphorylation / drug effects
  • Propiophenones / pharmacology*
  • Thyroid Neoplasms / pathology*

Substances

  • ASCL1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Flavonoids
  • Propiophenones
  • Mitogen-Activated Protein Kinase 3
  • xanthohumol