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
Date
03/17/2010Pubmed ID
20226902Pubmed Central ID
PMC2841322DOI
10.1016/j.amjsurg.2009.08.034Scopus ID
2-s2.0-77649300540 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
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.
Author List
Cook MR, Luo J, Ndiaye M, Chen H, Kunnimalaiyaan MMESH terms used to index this publication - Major topics in bold
Basic Helix-Loop-Helix Transcription FactorsCell Proliferation
Cells, Cultured
Drug Screening Assays, Antitumor
Flavonoids
Humans
Mitogen-Activated Protein Kinase 3
Phosphorylation
Propiophenones
Thyroid Neoplasms
