Doxorubicin exhibits strong and selective association with VEGF Pu22 G-quadruplex

Date

2020-12-01

Author

Bilgen, Ecenaz
Persil Çetinkol, Özgül

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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 Pu-22 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.

Subject Keywords

Biophysics, Biochemistry, Molecular Biology, Doxorubicin, Anthracycline, G-quadruplex, DNA, Cancer, VEGF

URI

https://hdl.handle.net/11511/57428

Journal

Biochimica et Biophysica Acta - General Subjects

DOI

https://doi.org/10.1016/j.bbagen.2020.129720

Collections

Department of Chemistry, Article

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Citation Formats

E. Bilgen and Ö. Persil Çetinkol, “Doxorubicin exhibits strong and selective association with VEGF Pu22 G-quadruplex,” Biochimica et Biophysica Acta - General Subjects, pp. 0–0, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/57428.