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Updated: May 9, 2026
12:19
Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Cyclic AMP-response element regulated cell cycle arrests in cancer cells
Ping Wang1, Shuaishuai Huang, Feng Wang
1Zhejiang Provincial Key Laboratory of Pathophysiology, Medical School, Ningbo University, Ningbo, China. pinoav@hotmail.com
Plos One
|July 11, 2013
Summary
Trichosanthin (TCS) induces cancer cell cycle arrest by blocking CREB binding to CRE, impacting proliferation genes. Combined TCS and CRE treatment reversed these arrests, highlighting a novel therapeutic pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Trichosanthin (TCS) inhibits cervical adenocarcinoma (HeLa) cell proliferation via the PKC/MAPK/CREB pathway.
- TCS down-regulates Bcl-2 expression, a process reversible by CRE decoy oligonucleotides (OGN) that block CRE-binding protein (CREB) binding.
- CRE-mediated gene expression is implicated in HeLa cell proliferation, but TCS effects on cell cycle arrest and CRE regulation remain unclear.
Purpose of the Study:
- To investigate the effect of TCS on cell cycle arrests in various cancer cell lines.
- To determine if genes involved in cell cycle regulation are modulated by CRE.
- To elucidate the role of CREB-mediated gene expression in TCS-induced cell cycle arrest.
Main Methods:
- Treatment of HeLa, Caski, C33a, and SW1990 cancer cells with TCS.
- Analysis of cell cycle phase distribution (S, G1, G2/M).
- Assessment of cyclin and cyclin-dependent kinase (CDK) expression levels.
- Combined treatment with TCS and CRE decoy oligonucleotides.
Main Results:
- TCS induced S, G1, and G2/M phase arrests, accompanied by down-regulation of cyclins (A, D1, E, B1) and CDKs (2, 4).
- These cell cycle arrests were reversed by co-treatment with TCS and CRE, leading to significant up-regulation of cyclin A and D1.
- TCS inhibits the binding of CREB to CRE on proliferation-related genes, inducing cancer cell cycle arrest.
Conclusions:
- TCS induces specific cell cycle arrests in cancer cells by inhibiting CREB binding to CRE.
- This mechanism affects genes crucial for cell proliferation.
- The findings suggest a novel therapeutic strategy involving TCS for cervical adenocarcinoma and potentially other cancers.
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