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

Date

2020-12-01

Author

Bilgen, Ecenaz
Persil Çetinkol, Özgül

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

319
views

0
downloads

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

Suggestions

OpenMETU
Core

Examination of the dielectrophoretic spectra of MCF7 breast cancer cells and leukocytes Çağlayan, Zeynep; Demircan Yalçın, Yağmur; Külah, Haluk (Wiley, 2020-03-01) The detection of circulating tumor cells (CTCs) in blood is crucial to assess metastatic progression and to guide therapy. Dielectrophoresis (DEP) is a powerful cell surface marker-free method that allows intrinsic dielectric properties of suspended cells to be exploited for CTC enrichment/isolation from blood. Design of a successful DEP-based CTC enrichment/isolation system requires that the DEP response of the targeted particles should accurately be known. This paper presents a DEP spectrum method to inve...
The serum immunoglobulin G glycosylation signature of gastric cancer Ruhaak, L. Renee; Barkauskas, Donald A.; Torres, Javier; Cooke, Cara L.; Wu, Lauren D.; Stroble, Carol; Özcan Kabasakal, Süreyya; Williams, Cynthia C.; Camorlinga, Margarita; Rocke, David M.; Lebrilla, Carlito B.; Solnick, Jay V. (Elsevier BV, 2015-03-01) Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). Serum IgG was released and analyzed using nano-LC–TOF mass spectrometry. Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG ...
Monoclonal antibodies for targeted therapy in colorectal cancer. Banerjee, Sreeparna (Informa UK Limited, 2010-04-15) Traditional therapeutic regimens of solid tumors such as chemotherapy and radiotherapy often do not distinguish between malignant and normal tissues, resulting in considerable side-effects. Monoclonal antibodies (mAbs), targeted against antigens dysregulated in cancers, have therefore generated great interest in both clinical and research settings. The antibodies are either chimeric or human(ized) and can bind to and inhibit target proteins overexpressed in both solid tumors and hematological malignancies. ...
Retinal vessel segmentation using convolutional neural networks Ulusoy, İlkay (2018-05-05) Retinal vessel segmentation and extracting features such as tortuosity, width, length related to those vessels can be used in diagnosis, treatment and screening of many diseases such as retinopathy of prematurity, hypertension and diabetes. Therefore, automatic segmentation of vessels by computers will make the analysis of those diseases easier and will help during the screening, diagnosis and treatment processes. In this study, a solution based on convolutional neural networks (CNN) is proposed for automat...
Multifaceted Transport Characteristics of Nanomedicine: Needs for Characterization in Dynamic Environment Özçelikkale, Altuğ; Han, Bumsoo (American Chemical Society (ACS), 2013-06-01) Nanomedicine for cancer, where nanoparticles (NPs) are used to deliver drugs, imaging agents, and heat to tumors, shows great potential of improved therapeutic outcomes. In spite of promising early stage results, its clinical efficacy is still significantly limited due to complex transport barriers in vivo. These transport barriers are associated with tumor microenvironment, which is highly complex and heterogeneous and varies spatiotemporally. Thus, in order to improve the in vivo efficacy of nanomedicine,...

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.