Faculty Collaboration Database

Resveratrol induces Notch2-mediated apoptosis and suppression of neuroendocrine markers in medullary thyroid cancer. Ann Surg Oncol 2011 May;18(5):1506-11

Date

12/25/2010

Pubmed ID

21184191

Pubmed Central ID

PMC3078954

DOI

10.1245/s10434-010-1488-z

Scopus ID

2-s2.0-79955824831 (requires institutional sign-in at Scopus site)   44 Citations

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.

Author List

Truong M, Cook MR, Pinchot SN, Kunnimalaiyaan M, Chen H

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents, Phytogenic
Apoptosis
Basic Helix-Loop-Helix Transcription Factors
Blotting, Western
Carcinoma, Medullary
Caspase 3
Cell Line, Tumor
Cell Proliferation
Chromogranin A
Humans
Neurosecretory Systems
Poly(ADP-ribose) Polymerases
RNA, Messenger
Receptor, Notch2
Reverse Transcriptase Polymerase Chain Reaction
Stilbenes
Thyroid Neoplasms