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

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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DOI:
10.1016/j.amjsurg.2009.08.034
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发表时间:
2010-03
影响因子:
3
通讯作者:
Kunnimalaiyaan, Muthusamy
Kunnimalaiyaan, Muthusamy
中科院分区:
医学3区
文献类型:
--
作者:
Cook, Mackenzie R.;Luo, Jie;Ndiaye, Mary;Chen, Herbert;Kunnimalaiyaan, Muthusamy

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Achaete-Scute Complex-Like 1(ASCL 1)是一种在甲状腺髓样癌(MTC)恶性发展中起重要作用的转录因子。Raf-1信号传导的激活与ASCL 1抑制和生长抑制相关。黄腐酚是一种天然化合物,最近已被证明具有抗癌特性。因此,我们假设黄腐酚将通过激活Raf-1信号传导抑制生长,从而改变MTC的恶性表型。用黄腐酚(0-30 μM)处理人MTC细胞长达6天。通过MTT比色测定来测量增殖。对ASCL 1和Raf-1途径活化的标志物进行蛋白质印迹分析。用黄腐酚处理MTC细胞导致生长的剂量依赖性抑制。此外,还观察到磷酸化ERK 1/2的诱导和ASCL 1蛋白的减少。黄腐酚是MTC细胞中有效的Raf-1激活剂。该化合物抑制MTC生长,改变恶性表型,并保证进一步的临床前研究。
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 anti-cancer properties. We thus hypothesized that Xanthohumol that would suppress growth by activating Raf-1 signaling, thus altering the malignant phenotype of MTC. Human MTC cells were treated with Xanthohumol (0–30 μM) for up to 6 days. Proliferation was measured by a MTT colorimetric assay. Western blot analysis was performed for ASCL1 and markers of Raf-1 pathway activation. 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. Xanthohumol is a potent Raf-1 activator in MTC cells. This compound suppresses MTC growth, alters the malignant phenotype and warrants further pre-clinical study.
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