Subramani Ramadevi, Chatterjee Animesh, Pedroza Diego A, Poudel Seeta, Rajkumar Preetha, Annabi Jeffrey, Penner Elizabeth, Lakshmanaswamy Rajkumar
Center of Emphasis in Cancer Research, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, TX, United States.
Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, United States.
Front Oncol. 2024 Sep 12;14:1371792. doi: 10.3389/fonc.2024.1371792. eCollection 2024.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with no effective targeted treatment currently available. Estrogen and its metabolites influence the growth of mammary cancer. Previously, we demonstrated the anti-cancer effects of 2-methoxyestradiol (2ME2) on mammary carcinogenesis.
In the present study, we investigated the effects of 2ME2 on TNBC cells. TNBC (MDA-MB-231 and MDA-MB-468) and non-tumorigenic breast (MCF10A) cell lines were used to determine the effects of 2ME2 on cell proliferation (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; MTS assay), cell cycle (flow cytometric assay), migration (transwell migration assay), invasion (matrigel invasion assay), apoptosis (annexin V/propidium iodide assay), colony formation (soft agar assay), and miRNome (human miRNA profiling array). The miRNome data were analyzed using the c-BioPortal and Xena platforms. Moreover, Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and reactome pathway analyses were performed.
We found that 2ME2 effectively inhibited cell proliferation and induced apoptosis. Furthermore, 2ME2 treatment arrested TNBC cells in the S-phase of the cell cycle. Treatment with 2ME2 also significantly decreased the aggressiveness of TNBC cells by inhibiting their migration and invasion. In addition, 2ME2 altered the miRNA expression in these cells. In silico analysis of the miRNome profile of 2ME2-treated MDA-MB-468 cells revealed that miRNAs altered the target genes involved in many different cancer hallmarks.
2ME2 inhibits triple negative breast cancer by impacting major cellular processes like proliferation, apoptosis, metastasis, etc. It further modifies gene expression by altering the miRNome of triple negative breast cancer cells. Overall, our findings suggest 2ME2 as a potent anti-cancer drug for the treatment of TNBC.
三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，目前尚无有效的靶向治疗方法。雌激素及其代谢产物会影响乳腺癌的生长。此前，我们已证明2-甲氧基雌二醇（2ME2）对乳腺癌发生具有抗癌作用。
在本研究中，我们调查了2ME2对TNBC细胞的影响。使用TNBC（MDA-MB-231和MDA-MB-468）和非致瘤性乳腺（MCF10A）细胞系来确定2ME2对细胞增殖（3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑；MTS法）、细胞周期（流式细胞术检测）、迁移（Transwell迁移试验）、侵袭（基质胶侵袭试验）、凋亡（膜联蛋白V/碘化丙啶检测）、集落形成（软琼脂试验）和微小RNA组（人类miRNA谱阵列）的影响。使用c-BioPortal和Xena平台对微小RNA组数据进行分析。此外，还进行了京都基因与基因组百科全书、基因本体论和反应组途径分析。
我们发现2ME2能有效抑制细胞增殖并诱导凋亡。此外，2ME2处理使TNBC细胞停滞在细胞周期的S期。用2ME2处理还通过抑制TNBC细胞的迁移和侵袭显著降低了其侵袭性。此外，2ME2改变了这些细胞中的miRNA表达。对经2ME2处理的MDA-MB-468细胞的微小RNA组谱进行的计算机分析表明，miRNA改变了涉及许多不同癌症特征的靶基因。
2ME2通过影响增殖、凋亡、转移等主要细胞过程来抑制三阴性乳腺癌。它还通过改变三阴性乳腺癌细胞的微小RNA组来进一步修饰基因表达。总体而言，我们的研究结果表明2ME2是一种用于治疗TNBC的有效抗癌药物。
