Annals of Surgical Oncology

, Volume 18, Issue 5, pp 1506–1511

Resveratrol Induces Notch2-Mediated Apoptosis and Suppression of Neuroendocrine Markers in Medullary Thyroid Cancer

  • Matthew Truong
  • Mackenzie R. Cook
  • Scott N. Pinchot
  • Muthusamy Kunnimalaiyaan
  • Herbert Chen
Translational Research and Biomarkers

DOI: 10.1245/s10434-010-1488-z

Cite this article as:
Truong, M., Cook, M.R., Pinchot, S.N. et al. Ann Surg Oncol (2011) 18: 1506. doi:10.1245/s10434-010-1488-z

Abstract

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.

Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Matthew Truong
    • 1
    • 2
  • Mackenzie R. Cook
    • 1
    • 2
  • Scott N. Pinchot
    • 1
    • 2
  • Muthusamy Kunnimalaiyaan
    • 1
    • 2
  • Herbert Chen
    • 1
    • 2
    • 3
  1. 1.Department of Surgery, Endocrine Research LaboratoryUniversity of WisconsinMadisonUSA
  2. 2.University of Wisconsin Carbone Cancer CenterMadisonUSA
  3. 3.H4/722 Clinical Science CenterUniversity of WisconsinMadisonUSA

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