Xanthohumol inhibits the neuroendocrine transcription factor achaete-scute complex-like 1, suppresses proliferation, and induces phosphorylated ERK1/2 in medullary thyroid cancer - 19/08/11
Corresponding author. Tel.: +1 608 265 4111Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : Medullary thyroid cancer, Neuroendocrine tumor, Achaete-scute complex-like 1, Phosphorylated ERK1/2, Xanthohumol
Plan
| 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.). |
Vol 199 - N° 3
P. 315-318 - mars 2010 Retour au numéro
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