Transcriptomic analysis of MCF7 breast cancer cells treated with MGBs reveals a profound inhibition of estrogen receptor genes

• Published in: Bioorganic chemistry 2024-10, Vol.151, p.107680, Article 107680
• Main Authors: Alniss, Hasan Y., Saber-Ayad, Maha M., Ramadan, Wafaa S., Manasa Bhamidimarri, Poorna, Msallam, Yousef A., Al-Jubeh, Hadeel M., Ravi, Anil, Menon, Varsha, Hamoudi, Rifat, El-Awady, Raafat
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Breast Cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Estrogen receptor (ER); Female; Gene Expression Profiling; Humans; Ligands; MCF-7 Cells; MCF7; Minor Groove Binder (MGB); Molecular Structure; Receptors, Estrogen - metabolism; Structure-Activity Relationship; Transcriptome - drug effects; Transcriptomic analysis; Tumor Cells, Cultured
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107680

[Display omitted] •Transcriptomic analysis was utilized to investigate the molecular mechanisms underlying MGB response in breast cancer cells.•Ligand 5 downregulated 34 out of the 35 genes that are associated with the estrogen receptor.•The observed multitarget activity of MGBs originates from their intervention at nucleic acids level.•MGBs can afford a viable therapeutic approach for direct inhibition of transcription factors. Breast cancer poses a significant health risk worldwide. However, the effectiveness of current chemotherapy is limited due to increasing drug resistance and side effects, making it crucial to develop new compounds with novel mechanism of action that can surpass these limitations. As a consequence of their reversible and targeted mechanism, DNA minor groove binders (MGBs) are considered as a relatively safer and more effective alternative. In this study, transcriptomic analysis was conducted to reveal the dysregulated genes and signaling pathways in MCF7 cancer cells following treatment with novel MGB ligands to gain insights into the mechanism of action of MGBs at the molecular level. The transcriptomic results were validated using real-time PCR. The findings of this study indicate that the investigated MGBs primarily inhibit the genes associated with the estrogen receptor. Remarkably, ligand 5 showed downregulation of 34 out of the 35 genes regulated by estrogen receptor, highlighting its potential as a promising candidate for breast cancer therapy.