De la Cruz-Cano Eduardo, González-Díaz José Ángel, Olivares-Corichi Ivonne María, Ayala-Sumuano Jorge Tonatiuh, Díaz-Gandarilla José Alfredo, Torres-Sauret Quirino, Larios-Serrato Violeta, Vilchis-Reyes Miguel Ángel, López-Victorio Carlos Javier, González-Garrido José Arnold, García-Sánchez José Rubén
Laboratorio de Bioquímica y Biología Molecular, División Académica de Ciencias Básicas, Centro de Investigación de Ciencia y Tecnología Aplicada de Tabasco (CICTAT), Universidad Juárez Autónoma de Tabasco, Cunduacán C.P. 86690, Mexico.
Laboratorio de Oncología Molecular y Estrés Oxidativo, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México C.P. 11340, Mexico.
Int J Mol Sci. 2025 Apr 12;26(8):3662. doi: 10.3390/ijms26083662.
Fluorinated chalcones are molecules reported to possess potent anticancer properties against triple-negative breast cancer (TNBC) cells. However, their molecular mechanisms have not yet been fully explored. Using bioinformatics tools, we analyzed the transcriptomes of MDA-MB-231 cells treated with either a novel fluorinated chalcone (compound ) or a control in order to identify differentially expressed (DE) genes associated with its anticancer activity and determine the biological processes in which these genes are involved. A fluorinated chalcone was synthesized using the Claisen-Schmidt method. The transcriptome of MDA-MB-231 cells was then analyzed on an Illumina NextSeq500, and DE genes with significant changes in expression were identified using the DESeq2 v1.38.0 bioinformatics tool under the strict detection criteria of |log2FC| ≥ 2 and adjusted < 0.05. We identified 504 DE genes, which were enriched in terms related to "regulation of cell death", "cation transport", "response to topologically incorrect proteins", and "response to unfolded proteins". Surprisingly, these genes were involved in "the HSF1-dependent transactivation pathway" and "the attenuation phase pathway". This bioinformatics-based study suggests that the tested fluorinated chalcone could influence HSF-1 silencing in addition to promoting the up-regulation of several genes involved in stress-induced apoptosis. Therefore, the tested compound could have enormous potential as a novel approach for TNBC treatment.
据报道，氟化查尔酮分子对三阴性乳腺癌（TNBC）细胞具有强大的抗癌特性。然而，它们的分子机制尚未得到充分探索。我们使用生物信息学工具分析了用新型氟化查尔酮（化合物）或对照处理的MDA-MB-231细胞的转录组，以鉴定与其抗癌活性相关的差异表达（DE）基因，并确定这些基因所涉及的生物学过程。使用克莱森-施密特方法合成了一种氟化查尔酮。然后在Illumina NextSeq500上分析MDA-MB-231细胞的转录组，并使用DESeq2 v1.38.0生物信息学工具在|log2FC|≥2和校正后<0.05的严格检测标准下鉴定表达有显著变化的DE基因。我们鉴定出504个DE基因，这些基因在与“细胞死亡调控”、“阳离子转运”、“对拓扑错误蛋白质的反应”和“对未折叠蛋白质的反应”相关的方面富集。令人惊讶的是，这些基因参与了“HSF1依赖性反式激活途径”和“衰减期途径”。这项基于生物信息学的研究表明，所测试的氟化查尔酮除了促进参与应激诱导凋亡的几个基因的上调外，还可能影响HSF-1沉默。因此，所测试的化合物作为TNBC治疗的新方法可能具有巨大潜力。
