Xanthohumol inhibits the neuroendocrine transcription factor achaete-scute complex-like 1, suppresses proliferation, and induces phosphorylated ERK1/2 in medullary thyroid cancer
Received 15 July 2009; received in revised form 9 August 2009
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 μmol/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.
Endocrine Surgery Research Laboratory, Department of Surgery, University of Wisconsin, Madison, WI, USA
Corresponding author. Tel.: +1 608 265 4111
Supported by the Howard Hughes Medical Research Institute (M.R.C.), NIH−R 21 CA117117 (H.C.), NIH−R01 CA109053 (H.C.), NIH–RO1 CA121115 (H.C.), American College of Surgeons, George H.A. Clowes Jr Memorial Research Career Development Award (H.C.), and Carcinoid Cancer Foundation Research Award (H.C.).
ABSTRACT