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Efficient iPS Cell Generation from Blood Using Episomes and HDAC Inhibitors
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Development of an Efficient Screening System for HDAC Inhibitor Based on TCF Response Element
Chen Pang1, Limeng Dai2, Gang He1
1Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Anti-Cancer Agents in Medicinal Chemistry
|November 1, 2018
Summary
A new cell-based screening system effectively identified novel compounds with histone deacetylase inhibitor (HDACi) activity. This system successfully pinpointed Wsu-18 as a potential anti-cancer agent from a natural products library.
Area of Science:
- Epigenetics and molecular oncology.
- Drug discovery and development.
Background:
- Histone acetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is crucial for gene expression.
- Aberrant histone acetylation is linked to cancer development and progression.
- Histone deacetylase inhibitors (HDACis) exhibit anti-cancer properties, including cell cycle arrest, apoptosis induction, and metastasis inhibition, with many currently in clinical trials.
Purpose of the Study:
- To develop and validate a cell-based screening system for identifying novel compounds with HDACi activity.
- To screen a natural products library for potential HDACis using the developed system.
Main Methods:
- A cell-based screening strategy was employed.
- The interaction between HDACs and TCFs was assessed using a reporter assay.
- A natural products library (A10) was screened in colon cancer cells.
Main Results:
- The screening system successfully identified compounds with HDACi activity based on HDAC-TCF interactions.
- A compound designated Wsu-18 was preliminarily identified as a potential HDACi from the A10 library.
Conclusions:
- The developed screening system is efficient and promising for identifying HDACis.
- The system is suitable for screening diverse small molecular chemical libraries for anti-cancer drug discovery.
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