Evaluation of the Anticancer Effects of DODP on Gene Expression and Oxidative Stress in Gastric Cancer: An Integrated Docking, Bioinformatics, and Experimental Approach

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Authors: Tuğba Ağbektaş, Hakki Coskun, Hüsnü Çağrı Genç, Gülcihan Cinar Kaya, Ayça Taş, Kenan Gören, Alakbar Huseynzada, Ruslan Guliyev, U. A. Hasanova, Savaş Kaya, Alejandro Morales‐Bayuelo, Yavuz Siliğ
Cited by: 3
References: 45

Abstract

(1) Background: Gastric cancer (GC) remains a major global health challenge due to its high heterogeneity and aggressive progression. The discovery of novel bioactive molecules with anticancer properties has, therefore, become a critical research focus. In this study, we synthesized and characterized 4,4′-(5,8-dioxa-2,11-diazadodecane-1,11-diene-1,12-diyl)diphenol (DODP) and evaluated its anticancer potential using molecular docking, bioinformatics, and experimental analyses. (2) Methods: The chemical structure of DODP was confirmed through 1H and 13C NMR spectroscopy. Molecular docking was conducted to examine the interaction of DODP with apoptosis and cell cycle-related proteins (TP53, MDM2, and MYC) and the immune checkpoint marker CD274 (PD-L1). Cytotoxicity against AGS GC cells was determined using the MTT assay at concentrations ranging from 0.01 to 50 µM, and gene expression alterations were analyzed by quantitative polymerase chain reaction (qPCR) and bioinformatics evaluation. (3) Results: NMR data verified the successful synthesis of DODP. The docking results indicated strong binding affinity, especially with TP53 and CD274. DODP showed notable cytotoxicity after 72 h of exposure and induced upregulation of TP53, MYC, and CD274 and downregulation of MDM2 in AGS cells. Although the patterns were consistent with cell-based and bioinformatic analyses, significant discriminatory ability in blood samples was observed only for MYC (AUC = 0.651; p = 0.044). (4) Conclusions: DODP influenced apoptosis-associated transcriptional responses in GC, offering early mechanistic evidence that should be evaluated in more comprehensive biological models.

Fields of Study & Subjects

Cancer-related Molecular Pathways Cancer Hypoxia and Metabolism Carcinogens and Genotoxicity Assessment

Publication details

Journal / source
Life
Publisher
MDPI AG
Volume
16
Issue
4
Pages
534–534
Publication date
24 March 2026
Language
EN