caa a22 4500 445336625 CHVBK 20180317142757.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1245/s10434-010-1488-z doi (NATIONALLICENCE)springer-10.1245/s10434-010-1488-z Resveratrol Induces Notch2-Mediated Apoptosis and Suppression of Neuroendocrine Markers in Medullary Thyroid Cancer [Elektronische Daten] [Matthew Truong, Mackenzie Cook, Scott Pinchot, Muthusamy Kunnimalaiyaan, Herbert Chen] Background: Currently, complete surgical resection is the only curative option for medullary thyroid cancer (MTC). Previous work has shown the Notch pathway is a potent tumor suppressor in MTC and that resveratrol activates the Notch pathway in carcinoid cancer, a related neuroedocrine malignancy. In this study, we hypothesized that the effects observed on carcinoid cells could be extended to MTC. Methods: MTC cells treated with varying doses of resveratrol were assayed for viability by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Western blot analysis for achaete-scute complex-like 1 (ASCL1), chromogranin A (CgA), full-length and cleaved caspase 3, and poly-ADP ribose polymerase (PARP) was performed. Quantitative real-time polymerase chain reaction (qPCR) was used to measure relative mRNA expression. Results: Treatment with resveratrol resulted in growth suppression and an increase in the cleavage of caspase-3 and PARP. A dose-dependent inhibition of ASCL1, a neuroedocrine transcription factor, was observed at the protein and mRNA levels. Protein levels of CgA, a marker of hormone secretion, were also reduced after treatment with resveratrol. A dose-dependent induction of Notch2 mRNA was observed by qPCR. Conclusions: Resveratrol suppresses in vitro growth, likely through apoptosis, as demonstrated by cleavage of caspase-3 and PARP. Furthermore, resveratrol decreased neuroedocrine markers ASCL1 and chromogranin A. Induction of Notch2 mRNA suggests that this pathway may be central in the anti-MTC effects observed. Society of Surgical Oncology, 2010 Truong Matthew Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut Cook Mackenzie Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut Pinchot Scott Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut Kunnimalaiyaan Muthusamy Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut Chen Herbert Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut Annals of Surgical Oncology Springer-Verlag 18/5(2011-05-01), 1506-1511 1068-9265 18:5<1506 2011 18 10434 https://doi.org/10.1245/s10434-010-1488-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-010-1488-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Truong Matthew Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut NATIONALLICENCE 700 1- Cook Mackenzie Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut NATIONALLICENCE 700 1- Pinchot Scott Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut NATIONALLICENCE 700 1- Kunnimalaiyaan Muthusamy Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut NATIONALLICENCE 700 1- Chen Herbert Department of Surgery, Endocrine Research Laboratory, University of Wisconsin, Madison, WI, USA aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/5(2011-05-01), 1506-1511 1068-9265 18:5<1506 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer