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 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 Pu G4 structure and the calculated association constant for VEGF Pu-G4 complex (K = 7.50 × 10) was very close to the reported K values for Dox-dsDNA complexes. Additionally, the competition dialysis experiments revealed the selectivity of Dox to Pu 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 Pu 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 Pu G4 might be one of the plausible mechanisms behind its anti-tumor activity.