黄腐酚抑制神经内分泌转录因子 Achaete-scute 复合物样 1，抑制增殖，并诱导甲状腺髓样癌细胞中磷酸化 ERK1/2。
Xanthohumol inhibits the neuroendocrine transcription factor achaete-scute complex-like 1, suppresses proliferation, and induces phosphorylated ERK1/2 in medullary thyroid cancer.
机构信息
Endocrine Surgery Research Laboratory, Department of Surgery, University of Wisconsin, Madison, WI, USA.
出版信息
Am J Surg. 2010 Mar;199(3):315-8; discussion 318. doi: 10.1016/j.amjsurg.2009.08.034.
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.
背景
Achaete-scute complex-like 1（ASCL1）是一种转录因子，在髓样甲状腺癌（MTC）的恶性发展中起着重要作用。Raf-1 信号的激活与 ASCL1 的抑制和生长抑制有关。黄烷醇，一种天然化合物，最近被证明具有抗癌特性。因此，我们假设黄烷醇通过激活 Raf-1 信号通路来抑制生长，从而改变 MTC 的恶性表型。
方法
用黄烷醇（0-30 微摩尔/升）处理人 MTC 细胞长达 6 天。通过甲基噻唑基二苯基四唑溴盐（MTT）比色法测量增殖。进行 Western blot 分析以检测 ASCL1 和 Raf-1 通路激活标志物。
结果
黄烷醇处理 MTC 细胞导致生长呈剂量依赖性抑制。此外，还观察到磷酸化 ERK1/2 的诱导和 ASCL1 蛋白的减少。
结论
黄烷醇是 MTC 细胞中一种有效的 Raf-1 激活剂。该化合物抑制 MTC 生长，改变恶性表型，值得进一步进行临床前研究。
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