College of Pharmacy, Department of Medicinal Chemistry, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates.
Bioorg Chem. 2024 Oct;151:107680. doi: 10.1016/j.bioorg.2024.107680. Epub 2024 Jul 27.
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.
乳腺癌是全球范围内一个重大的健康风险。然而，由于药物耐药性和副作用的增加，当前化疗的效果受到限制，因此开发具有新作用机制的新化合物至关重要，这些化合物可以克服这些限制。由于其可逆和靶向作用机制，DNA 小沟结合物 (MGBs) 被认为是一种相对更安全、更有效的替代药物。在这项研究中，通过转录组分析揭示了 MCF7 癌细胞在新型 MGB 配体处理后的失调基因和信号通路，深入了解 MGB 分子水平上的作用机制。使用实时 PCR 对转录组结果进行了验证。本研究的结果表明，所研究的 MGB 主要抑制与雌激素受体相关的基因。值得注意的是，配体 5 下调了 35 个受雌激素受体调节的基因中的 34 个，这突出了其作为治疗乳腺癌的有前途的候选药物的潜力。
