Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo

Anaplastic thyroid cancer (ATC) is a very aggressive thyroid gland malignancy with very poor prognosis. It is suspected 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.

[1]  A. Capobianco,et al.  Notchic-ER chimeras display hormone-dependent transformation, nuclear accumulation, phosphorylation and CBF1 activation , 2000, Oncogene.

[2]  P. Krammer,et al.  Wogonin and Related Natural Flavones Overcome Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Protein Resistance of Tumors by Down-regulation of c-FLIP Protein and Up-regulation of TRAIL Receptor 2 Expression* , 2011, The Journal of Biological Chemistry.

[3]  Daan Brandenbarg.  The National. , 1892 .

[4]  I. Pinchuk,et al.  Flavonoids Induce Apoptosis in Human Leukemia U937 Cells Through Caspase- and Caspase-Calpain-Dependent Pathways , 2004, Nutrition and cancer.

[5]  Xianglin Shi,et al.  Chrysin inhibits expression of hypoxia-inducible factor-1α through reducing hypoxia-inducible factor-1α stability and inhibiting its protein synthesis , 2007, Molecular Cancer Therapeutics.

[6]  Herb Chen,et al.  Notch in the development of thyroid C-cells and the treatment of medullary thyroid cancer. , 2010, American journal of translational research.

[7]  Herb Chen,et al.  Identification and validation of Notch pathway activating compounds through a novel high‐throughput screening method , 2011, Cancer.

[8]  B. Nelkin,et al.  Dual inhibition of mitogen-activated protein kinase kinase and mammalian target of rapamycin in differentiated and anaplastic thyroid cancer. , 2009, The Journal of clinical endocrinology and metabolism.

[9]  K. Landis-Piwowar,et al.  Relationship between the methylation status of dietary flavonoids and their growth‐inhibitory and apoptosis‐inducing activities in human cancer cells , 2008, Journal of cellular biochemistry.

[10]  Herb Chen,et al.  Valproic Acid Activates Notch1 Signaling and Induces Apoptosis in Medullary Thyroid Cancer Cells , 2008, Annals of surgery.

[11]  O. Ozaki,et al.  Immediate causes of death in thyroid carcinoma: clinicopathological analysis of 161 fatal cases. , 1999, The Journal of clinical endocrinology and metabolism.

[12]  J. Aster,et al.  Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. , 2005, Blood.

[13]  Iannis Aifantis,et al.  Oncogenic and tumor suppressor functions of Notch in cancer: it’s NOTCH what you think , 2011, The Journal of experimental medicine.

[14]  Xianglin Shi,et al.  Chrysin inhibits expression of hypoxia-inducible factor-1alpha through reducing hypoxia-inducible factor-1alpha stability and inhibiting its protein synthesis. , 2007, Molecular cancer therapeutics.

[15]  J. Hsieh,et al.  Truncated mammalian Notch1 activates CBF1/RBPJk-repressed genes by a mechanism resembling that of Epstein-Barr virus EBNA2 , 1996, Molecular and cellular biology.

[16]  J. McMurray,et al.  Notch/HES1-mediated PARP1 activation: a cell type-specific mechanism for tumor suppression. , 2011, Blood.

[17]  J. Sklar,et al.  TAN-1, the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms , 1991, Cell.

[18]  R. Kovall.  More complicated than it looks: assembly of Notch pathway transcription complexes , 2008, Oncogene.

[19]  Wen-Hsien Liu,et al.  Notch inhibits apoptosis by direct interference with XIAP ubiquitination and degradation , 2007, The EMBO journal.

[20]  Herb Chen,et al.  Antiproliferative effect of chrysin on anaplastic thyroid cancer. , 2011, The Journal of surgical research.

[21]  I. Screpanti,et al.  Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors. , 2008, The Journal of clinical endocrinology and metabolism.

[22]  S. Thorgeirsson,et al.  Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway , 2011, The Journal of experimental medicine.

[23]  R. Klein,et al.  Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. , 2004, Developmental biology.

[24]  Christopher Korch,et al.  Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and misidentification. , 2008, The Journal of clinical endocrinology and metabolism.

[25]  Herb Chen,et al.  Overexpression of the NOTCH1 Intracellular Domain Inhibits Cell Proliferation and Alters the Neuroendocrine Phenotype of Medullary Thyroid Cancer Cells* , 2006, Journal of Biological Chemistry.

[26]  Kuang-Tai Kuo,et al.  Reversal of inflammation‐associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysin , 2007, International journal of cancer.

[27]  I. Fleming,et al.  A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985‐1995 , 1998, Cancer.

[28]  S. Bray.  Notch signalling: a simple pathway becomes complex , 2006, Nature Reviews Molecular Cell Biology.

[29]  Herb Chen,et al.  Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. , 2006, Surgery.

[30]  Herb Chen,et al.  Notch1 mediates growth suppression of papillary and follicular thyroid cancer cells by histone deacetylase inhibitors , 2009, Molecular Cancer Therapeutics.

[31]  Hans Clevers,et al.  Notch1 functions as a tumor suppressor in mouse skin , 2003, Nature Genetics.

[32]  Raphael Kopan,et al.  The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism , 2009, Cell.