Salama Mohammed, Elamin Ahmed, Youssif Magda, Mattar Noura A
Department of Histochemistry and Cell Biology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Ultrastruct Pathol. 2025 Mar 4;49(2):158-169. doi: 10.1080/01913123.2025.2454691. Epub 2025 Jan 17.
Breast cancer patients experience more severe emotional distress and depression compared to those with other cancers. Selective serotonin reuptake inhibitors (SSRIs), like citalopram, are commonly used to treat depression. However, the link between SSRI use and breast cancer progression is debated. This study examined the cytotoxic effects of citalopram on triple-negative (MDA-MB231) and ER-positive (MCF-7) breast cancer cells. Results showed a significant decrease in cell viability in both cell lines following citalopram treatment. Interestingly, flow cytometry analysis revealed increased apoptotic cells and induction of cell cycle arrest upon treatment of the cells with citalopram. MCF-7 cells were arrested in the sub-G0-G1 phase, while MDA-MB231 cells accumulated in the S phase. Gene expression analysis demonstrated increased Bax expression and decreased Bcl2 levels. Moreover, cytochrome c and NF-κB were upregulated upon treatment with citalopram. Furthermore, transmission electron microscopy (TEM) analysis of treated cells showed apoptotic morphological changes including shrunken nuclei, membrane blebbing, and chromatin condensation with prominent appearance of autophagosomes and autolysosomes. Additionally, GADD45a and p21, involved in growth arrest and DNA damage, were significantly upregulated. In conclusion, citalopram's ability to induce apoptosis and alter cell cycle suggests its potential in breast cancer treatment.
与其他癌症患者相比，乳腺癌患者经历更严重的情绪困扰和抑郁。选择性5-羟色胺再摄取抑制剂（SSRI），如西酞普兰，常用于治疗抑郁症。然而，使用SSRI与乳腺癌进展之间的联系存在争议。本研究检测了西酞普兰对三阴性（MDA-MB231）和雌激素受体阳性（MCF-7）乳腺癌细胞的细胞毒性作用。结果显示，西酞普兰处理后，两种细胞系的细胞活力均显著下降。有趣的是，流式细胞术分析显示，用西酞普兰处理细胞后，凋亡细胞增加，细胞周期停滞。MCF-7细胞停滞在亚G0-G1期，而MDA-MB231细胞在S期积累。基因表达分析表明，Bax表达增加，Bcl2水平降低。此外，用西酞普兰处理后，细胞色素c和核因子κB上调。此外，对处理过的细胞进行透射电子显微镜（TEM）分析显示，细胞出现凋亡形态变化，包括细胞核缩小、膜泡形成和染色质浓缩，同时自噬体和自溶酶体明显出现。此外，参与生长停滞和DNA损伤的GADD45a和p21显著上调。总之，西酞普兰诱导凋亡和改变细胞周期的能力表明其在乳腺癌治疗中的潜力。
