Related Experiment Video
Updated: Dec 10, 2025
Analysis of Targeted Viral Protein Nanoparticles Delivered to HER2+ Tumors
Published on: June 18, 2013
Doxorubicin exhibits strong and selective association with VEGF Pu22 G-quadruplex
Ecenaz Bilgen1, Özgül Persil Çetinkol1
1Department of Chemistry, Middle East Technical University, 06800, Çankaya, Ankara, Turkey.
Background:
Vascular endothelial growth factor (VEGF), is upregulated in tumor cells and thus became a potential therapeutic target for anti-cancer drugs. Recent reports suggested the use of Doxorubicin (Dox) with VEGF-targeting siRNAs for an enhanced decrease in VEGF expression. Besides, VEGF-B gene therapy was found to suppress the cardiotoxicity effects of Dox. On the other hand, even though Dox is a commonly used anti-cancer agent, its mechanism of actions isn't completely mapped out. Herein, the interactions between a G4 structure formed by the VEGF promoter region Pu22 and Dox were investigated.
Methods:
The Dox-G4 interactions were examined via competition dialysis, UV-vis Absorption, Circular Dichroism (CD) and Fluorescence spectroscopy.
Results:
The results demonstrated that Dox was stabilizing the VEGF Pu22 G4 structure and the calculated association constant for VEGF Pu22-G4 complex (Ka = 7.50 × 106) was very close to the reported Ka values for Dox-dsDNA complexes. Additionally, the competition dialysis experiments revealed the selectivity of Dox to Pu22 compared to other G4 structures formed in telomeric repeats and promoter regions such as BCL-2 and C-myc.
Conclusions:
Dox exhibits strong and selective association with VEGF Pu22 G4 structure that was comparable to its well-known association with dsDNA.
General Significance:
The results presented here might be useful in the general area of antitumor drug-DNA interactions. Doxorubicin's significant affinity to VEGF Pu22 G4 might be one of the plausible mechanisms behind its anti-tumor activity.
Insights
Doxorubicin (Dox) selectively binds to a specific G4 structure in the VEGF promoter, similar to its DNA interactions. This finding may explain Doxorubicin's anti-tumor effects by targeting VEGF.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Vascular endothelial growth factor (VEGF) is upregulated in tumors, making it a therapeutic target.
- Doxorubicin (Dox) is an anti-cancer drug with incompletely understood mechanisms.
- VEGF-targeting siRNAs and VEGF-B gene therapy show potential in enhancing anti-cancer effects and reducing Dox cardiotoxicity.
Purpose of the Study:
- To investigate the interactions between Doxorubicin and a G-quadruplex (G4) structure in the VEGF promoter region (Pu22).
- To determine the binding affinity and selectivity of Doxorubicin to the VEGF Pu22 G4 structure.
Main Methods:
- Competition dialysis
- UV-vis Absorption spectroscopy
- Circular Dichroism (CD) spectroscopy
- Fluorescence spectroscopy
Main Results:
- Doxorubicin stabilizes the VEGF Pu22 G4 structure.
- The association constant (Ka) for Dox-VEGF Pu22 G4 complex is 7.50 × 10^6, comparable to Dox-dsDNA interactions.
- Doxorubicin shows selectivity for VEGF Pu22 G4 over other G4 structures (BCL-2, C-myc).
Conclusions:
- Doxorubicin exhibits strong and selective binding to the VEGF Pu22 G4 structure.
- This interaction may contribute to Doxorubicin's anti-tumor activity by targeting VEGF.
More Related Videos
04:48Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
08:57Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
Published on: October 5, 2017