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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
G-quadruplexes induce apoptosis in tumor cells
Haiyan Qi1, Chao-Po Lin, Xuan Fu
1Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. qiha@umdnj.edu
Cancer Research
|December 21, 2006
Summary
G-rich oligodeoxynucleotides (ODNs) that form G-quadruplexes induce tumor cell death via apoptosis. This process is dependent on ataxia telangiectasia mutated (ATM) and c-Jun NH2-terminal kinase (JNK) pathways.
Area of Science:
- Molecular Biology
- Cancer Research
- Oligonucleotide Therapeutics
Background:
- G-rich oligodeoxynucleotides (ODNs) form G-quadruplex structures.
- These G-quadruplex ODNs (GQ-ODNs) show antiproliferative and antitumor effects.
- The precise molecular mechanisms underlying their antitumor activity are not fully understood.
Purpose of the Study:
- To investigate the antiproliferative activity of telomeric G-tail ODNs (TG-ODNs) against tumor cells.
- To elucidate the molecular basis of TG-ODN-induced apoptosis.
- To explore the role of G-quadruplex conformation in TG-ODN activity.
Main Methods:
- Antiproliferative assays on various tumor cell lines.
- Systematic mutational analysis of TG-ODNs.
- Assessment of apoptosis markers (caspase activation, phosphatidylserine flipping).
- Investigation of the involvement of ataxia telangiectasia mutated (ATM) and c-Jun NH2-terminal kinase (JNK) pathways.
Main Results:
- TG-ODNs demonstrated significant antiproliferative activity, dependent on G-quadruplex formation.
- TG-ODNs induced apoptosis through caspase activation and phosphatidylserine flipping.
- Apoptosis was largely dependent on ATM and activated the JNK pathway.
- Nontelomeric GQ-ODNs also induced ATM/JNK-dependent apoptosis.
Conclusions:
- G-quadruplex conformation is crucial for the antiproliferative activity of TG-ODNs.
- TG-ODNs induce apoptosis via a pathway involving ATM and JNK.
- GQ-ODNs may share a common mechanism for tumor cell killing through ATM/JNK-dependent apoptosis.
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