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

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

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1
Endocrine Surgery Research Laboratory, Department of Surgery, University of Wisconsin, Madison, WI, USA.

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.

PMID:
20226902
PMCID:
PMC2841322
DOI:
10.1016/j.amjsurg.2009.08.034
[Indexed for MEDLINE]
Free PMC Article
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