Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo.
Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo.
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DOI：
10.1002/cncr.27742
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发表时间：
2013-02-15
期刊：
影响因子：
6.2
通讯作者：
Chen, Herbert
中科院分区：
文献类型：
--
作者：
Yu, Xiao-Min;TramAnh Phan;Patel, Priyesh N.;Jaskula-Sztul, Renata;Chen, Herbert
Anaplastic thyroid cancer (ATC) is a very aggressive thyroid gland malignancy with very poor prognosis. We suspect that the Notch signaling pathway, which is not active in ATC, may have a tumor suppressor function in this neoplasm. However, it remains unknown whether activation of Notch can yield therapeutic efficacies in ATC. The purpose of this study was to evaluate the effect of chrysin, a potential Notch inducer identified via high-throughput screening (HTS), on ATC both in vitro and in vivo. Chrysin treatment of ATC cells led to a dose-dependent inhibition of cellular growth. Protein and mRNA levels of Notch1 and Hes1, a down-stream Notch1 effector, were both up-regulated with treatment. Luciferase reporter assays incorporating the CBF1 binding site also confirmed the functional activity of chrysin-induced Notch1. Oral administration of chrysin suppressed the growth of ATC xenografts by an average of 59% compared with the vehicle control group (p=0.002). Additionally, calculated median time to tumor progression was 11 days for control mice and 21 days for chrysin treatment group (p=0.008). Analysis of chrysin-treated ATC tumors revealed an increase in the active intracellular domain of Notch1 protein. Activation of Notch1 in vivo was associated with the induction of cleaved Poly ADP-ribose polymerase protein, indicating that the growth inhibition was due to apoptosis. The novel Notch1 activator chrysin inhibits tumor growth in ATC both in vitro and in vivo. Chrysin could be a promising therapeutic candidate for ATC, and justifies further clinical studies.
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影响因子：
9
作者：
Greenblatt, David Yu;Cayo, Max A.;Chen, Herbert
通讯作者：
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影响因子：
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DOI：
10.1084/jem.20110198
发表时间：
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期刊：
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影响因子：
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