Xanthohumol inhibits the neuroendocrine transcription factor achaete-scute complex-like 1, suppresses proliferation, and induces phosphorylated ERK1/2 in medullary thyroid cancer.
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.
Cook
Mackenzie R
MR
Endocrine Surgery Research Laboratory, Department of Surgery, University of Wisconsin, Madison, WI, USA.
Luo
Jie
J
Ndiaye
Mary
M
Chen
Herbert
H
Kunnimalaiyaan
Muthusamy
M
D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011427:Propiophenones / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000473:pathology*
D051792:Basic Helix-Loop-Helix Proteins; D005419:Flavonoids; D048052:Mitogen-Activated Protein Kinase 3; D011427:Propiophenones; C065500:ASCL1 protein, human; C104536:xanthohumol