Related Experiment Video
Updated: Jun 3, 2026
09:44
High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
Identification and validation of Notch pathway activating compounds through a novel high-throughput screening method
Scott N Pinchot1, Renata Jaskula-Sztul, Li Ning
1Endocrine Surgery Research Laboratory, Department of Surgery and the University of Wisconsin Carbone Cancer Center, Madison, Wisconsin 53792, USA.
Cancer
|March 23, 2011
Summary
High-throughput screening identified resveratrol as a compound that activates Notch signaling. This activation suppresses carcinoid tumor growth and hormone production, offering a potential new treatment strategy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Carcinoid tumors are neuroendocrine (NE) neoplasms with limited therapeutic options.
- Notch pathway activation demonstrates potential for suppressing carcinoid cell growth and hormone secretion.
Purpose of the Study:
- To establish a high-throughput screening (HTS) process for identifying Notch-activating compounds.
- To validate the efficacy of resveratrol (RESV), the strongest compound identified, in carcinoid cells.
Main Methods:
- Utilized HTS to analyze 7264 compounds for Notch pathway activation.
- Employed cell-based assays, including luciferase reporter assays and immunoblotting, to assess pathway modulation and cellular effects.
- Conducted flow cytometry and RNA interference assays to elucidate mechanisms of action.
Main Results:
- Resveratrol (RESV) treatment upregulated Notch signaling, evidenced by suppressed expression of its target gene, achaete-scute complex-like 1.
- RESV induced a dose-dependent inhibition of carcinoid cell proliferation via S phase cell cycle arrest, confirmed by markers like p21Cip1/Waf.
- RESV suppressed the production of neuroendocrine peptides, including chromogranin A and serotonin, mediated by Notch2 isoform upregulation.
Conclusions:
- High-throughput screening is effective for discovering novel Notch-activating compounds for carcinoid therapy.
- Resveratrol demonstrates potential as a therapeutic agent for carcinoid tumors by inhibiting growth and hormone production.
- Targeting the Notch pathway offers a promising strategy to manage carcinoid tumors and associated endocrinopathies.
More Related Videos
Related Concept Videos
01:18Patch Clamp
Many fundamental cell functions such as muscle contraction and nerve transmission rely on the electrical signals produced by the movement of positively and negatively charged ions across the cell membrane. One competent method to record current flowing across the whole cell or single ion channel is the patch-clamp technique.
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...