Experimental cell research最新文献

{"title":"ALKBH5 promotes T-cell acute lymphoblastic leukemia growth via m6A-guided epigenetic inhibition of miR-20a-5p","authors":"Jiazhuo Liu ,&nbsp;Xin Zhang ,&nbsp;Yi Liao ,&nbsp;Chunlan Zhang ,&nbsp;Leiwen Peng","doi":"10.1016/j.yexcr.2024.114293","DOIUrl":"10.1016/j.yexcr.2024.114293","url":null,"abstract":"<div><div>This study investigates the role of ALKBH5-mediated m⁶A demethylation in T-cell acute lymphoblastic leukemia (T-ALL). T-ALL cell lines (HPB-ALL, MOLT4, Jurkat, CCRF-CEM) and human T cells were analyzed. CCRF-CEM and Jurkat cells were transfected with si-ALKBH5, miR-20a-5p-inhibitor, and pcDNA3.1-DDX5. The expression levels of <em>ALKBH5</em>, <em>miR-20a-5p</em>, and <em>DDX5</em> in these cells were determined using qRT-PCR and Western blotting. Cell viability, proliferation, colony formation, and apoptosis were assessed using CCK-8, EdU staining, colony formation assay, and flow cytometry. mRNA m6A levels were quantified with an m6A RNA methylation detection reagent, and RNA immunoprecipitation was employed to measure the enrichment of DGCR8 and m6A on the primary transcript <em>pri-miR-20a</em> of <em>miR-20a-5p</em>. Dual-luciferase assay confirmed the binding relationship between <em>miR-20a-5p</em> and <em>DDX5</em>. Results showed that <em>ALKBH5</em> and <em>DDX5</em> were upregulated in T-ALL tissues and cells, whereas <em>miR-20a-5p</em> was downregulated. Silencing <em>ALKBH5</em> inhibited T-ALL cell viability, colony formation, and proliferation, while promoting apoptosis. These effects were reversed by <em>miR-20a-5p</em> inhibition or <em>DDX5</em> overexpression. ALKBH5 reduced the relative m⁶A level in T-ALL cells and decreased <em>miR-20a-5p</em> expression by reducing DGCR8 binding to <em>pri-miR-20a-5p. miR-20a-5p</em> suppressed <em>DDX5</em> transcription. In conclusion, ALKBH5-mediated m⁶A demethylation decreases DGCR8 binding to <em>pri-miR-20a</em>, thereby repressing <em>miR-20a-5p</em> expression and enhancing <em>DDX5</em> expression, ultimately inhibiting T-ALL cell apoptosis and promoting proliferation.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114293"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling the extracellular vesicles of two human placenta-derived mesenchymal stromal cell populations","authors":"Ramin Khanabdali ,&nbsp;Mozhgan Shojaee ,&nbsp;Jancy Johnson ,&nbsp;Sam Q.K. Law ,&nbsp;Melissa B.L. Lim ,&nbsp;Patrick F. James ,&nbsp;Angus Tester ,&nbsp;Bill Kalionis","doi":"10.1016/j.yexcr.2024.114387","DOIUrl":"10.1016/j.yexcr.2024.114387","url":null,"abstract":"<div><div>Increasing evidence shows extracellular vesicles (EVs) are primarily responsible for the beneficial effects of cell-based therapies. EVs derived from mesenchymal stromal cells (MSCs) show promise as a source of EVs for cell-free therapies. The human placental fetal–maternal interface is a rich and abundant source of MSCs from which EVs can be isolated. This study focusses on chorionic MSCs (CMSC) located on the fetal aspect of the interface and decidual MSCs (DMSC) on the maternal aspect. This study used Ligand-based Exosome Affinity Purification (LEAP) chromatography to isolate EVs from well-characterized placental hTERT-transduced CMSC29 and DMSC23 cell lines, which retain many important stem cell-like properties of primary CMSC and DMSC, respectively. After initial biophysical characterization of the EVs isolated from each cell line, the biological activities and the protein, lipid and small RNA contents of CMSC29-EVs and DMSC23-EVs were compared and assessed.</div><div>LEAP-purified EVs from both sources were validated at the biophysical level by Spectradyne, Cryo-Transmission Electron Microscopy (Cryo-TEM), and Western blot analysis. EVs from each type were labelled with the live cell stain PKH26 and their <em>in vitro</em> uptake and internalization by human dermal fibroblast cells was assessed, as well as their phosphorylation of the protein kinase B/AKT (AKT) pathway. The protein and lipid contents were analyzed by mass spectrometry and the nucleic acid content by RNA sequencing (RNA-seq). Lastly, the biological activities of the EVs were evaluated in a BioMAP® Diversity PLUS® screen system across a panel of 12 human primary cell-based systems and <em>in vitro</em> cell proliferation.</div><div>EVs isolated from both DMSC23 and CMSC29 significantly increased proliferation of fibroblasts and showed phosphorylation of the AKT pathway. Protein mass spectrometry analysis identified a large number of proteins including cell surface receptors, cytokines, chemokines, matrix molecules and enzymes in both EV types. Lipidomic analysis identified species including phosphatidylcholine, triacylglycerides and diacylglycerides in both DMSC23 and CMSC29-derived EVs. There were some significant differences in identified microRNAs (miRNAs) between the two EV types. The top differentially expressed miRNAs between the two EV types show pathways association with matrix interaction, transcriptional regulation, proliferation, cellular protein modification processes, and vasculogenesis. Differences were also detected between DMSC23- and CMSC29-EVs in the biological activity they displayed in the BioMAP® Diversity PLUS® screen.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114387"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ganoderma lucidum extract reverses multidrug resistance in breast cancer cells through inhibiting ATPase activity of the P-glycoprotein via MAPK/ERK signaling pathway","authors":"Chunwei Jiao ,&nbsp;Jinshou Qiu ,&nbsp;Congcong Gong ,&nbsp;Xiaoyi Li ,&nbsp;Huijia Liang ,&nbsp;Chunyan He ,&nbsp;Sien Cen ,&nbsp;Yizhen Xie","doi":"10.1016/j.yexcr.2024.114355","DOIUrl":"10.1016/j.yexcr.2024.114355","url":null,"abstract":"<div><div>Breast cancer represents a persistent global health challenge, with multidrug resistance (MDR) posing a significant obstacle to effective treatment. In this study, we investigate the potential of <em>Ganoderma lucidum</em> extract (GLE) in reversing MDR in breast cancer and delve into the underlying mechanisms. We establish a robust in vitro 3D model of breast cancer with acquired MDR induced by paclitaxel. Utilizing the CCK-8 method, we assess the impact of GLE on cytotoxic drug sensitivity to determine its in vitro MDR reversal activity.</div><div>Our results reveal that GLE enhances the toxicity of paclitaxel in breast cancer cells by inhibiting the ATPase activity of P-glycoprotein (P-gp) and increasing the intracellular and extracellular excretion of P-gp substrates, all without significantly altering P-gp protein expression. Additionally, GLE inhibits the phosphorylation of ERK1/2, suggesting that the enhanced sensitivity of breast cancer cells to paclitaxel by GLE is associated with the MAPK pathway. These findings indicate that GLE may inhibit P-gp-mediated drug efflux via the MAPK pathway, thus effectively overcoming paclitaxel resistance in breast cancer.</div><div>This study provides valuable insights into the potential clinical applications of GLE in reversing multidrug resistance, offering hope for improved breast cancer treatment strategies.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114355"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anillin knockdown in the Drosophila nervous system shows locomotor and learning defects","authors":"Man Anh Huynh ,&nbsp;Dang Thi Phuong Thao ,&nbsp;Hideki Yoshida","doi":"10.1016/j.yexcr.2024.114364","DOIUrl":"10.1016/j.yexcr.2024.114364","url":null,"abstract":"<div><div>Anillin (Ani) is an evolutionarily conserved protein with a multi-domain structure that cross-links cytoskeletal proteins and plays an essential role in the formation of the contractile ring during cytokinesis. However, Ani is highly expressed in the human central nervous system (CNS), and it scaffolds myelin in the CNS of mice and modulates neuronal migration and growth in <em>Caenorhabditis elegans</em>. Although Ani is also highly expressed in the <em>Drosophila</em> CNS, its role remains unclear. In the present study, we showed that Ani is not only highly expressed in larval neuroblasts of the CNS, but also weakly expressed in the neuromuscular junction (NMJ) and axons. In addition, the <em>ani</em> knockdown in the nervous system led to pupal lethality, larval locomotor defects, and learning disability, along with abnormal morphology of the NMJ and distribution patterns of the mature neuropil in the CNS. These results show that Ani plays an important role also in the <em>Drosophila</em> nervous system.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114364"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small RNA sequencing of differentiated astrocytoma exposed to NMOSD patient sera reveals perturbations in neurodegenerative signaling","authors":"Pallavi Chatterjee ,&nbsp;Shouvik Chakravarty ,&nbsp;Nidhan K. Biswas ,&nbsp;Santosh Trivedi ,&nbsp;Ashis Datta ,&nbsp;Debashis Mukhopadhyay","doi":"10.1016/j.yexcr.2024.114375","DOIUrl":"10.1016/j.yexcr.2024.114375","url":null,"abstract":"<div><div>The signaling pathways behind severe astrocytic lysis with Aquaporin4 auto-antibody (AQP4-IgG) seropositivity, and reactive astrocytosis with myelin oligodendrocyte glycoprotein auto-antibody (MOG-IgG) seropositivity, remain largely unexplored in Neuromyelitis optica spectrum disorder (NMOSD), while almost no molecular details being known about double-seronegative (DN) patients. Recent discovery of glial fibrillary acidic protein (GFAP) in DN NMOSD patients’ cerebrospinal fluid, akin to AQP4-IgG + ve cases, suggests astrocytopathy. Here, we aim to study small non coding RNA (sncRNA) signature alterations in astrocytes exposed to AQP4-IgG + ve and MOG-IgG + ve patient sera, and their potential resemblance with DN-NMOSD. Next Generation Sequencing (NGS) revealed differential expression of several microRNAs with notable alterations in hsa-miR-6824-3p, hsa-miR-324-5p and hsa-miR-4466 respectively upon sera treatment. Results with DN-NMOSD patient sera are majorly similar to that of AQP4+ve sera. Strikingly, in all three treatments, hsa-miR-200b-3p was significantly upregulated. Functional enrichment analysis revealed that Hippo and FoxO signaling pathways were primarily impacted in AQP4-IgG + ve and double negative sera treated cells whereas, MOG-IgG + ve sera treatment perturbed the PI3K-Akt and MAPK signaling pathways. Furthermore, NGS also revealed differential expression of several piRNAs in cells upon treatment with AQP4-IgG + ve and MOG-IgG + ve sera and VEGF signaling was identified as the common target of differentially expressed piRNAs of both the groups. This study, for the first time, revealed that the molecular pathophysiology of double-seronegative NMOSD might involve astrocytopathy akin to AQP4+ve NMOSD, thus pointing towards the possible existence of unidentified astrocytic autoimmune targets and identified the major alterations in intracellular sncRNAs and the associated overall cellular signaling pathways that potentially contribute to the fate of astrocytes during the progression of the disease.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114375"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of THBS1 axis contributes to the antitumor effect of PA-MSHA in anaplastic thyroid cancer","authors":"Zhe Li ,&nbsp;Ting He ,&nbsp;Zhichao Xing ,&nbsp;Jingqiang Zhu ,&nbsp;Wenshuang Wu ,&nbsp;Anping Su","doi":"10.1016/j.yexcr.2024.114373","DOIUrl":"10.1016/j.yexcr.2024.114373","url":null,"abstract":"<div><div>Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, has the worst prognosis, and lacks effective treatment in clinical practice. Thrombospondin-1 (THBS1) is a multifunctional extracellular matrix (ECM) glycoprotein that regulates cell proliferation, apoptosis, and metastasis, and is considered a potential clinical biomarker for the monitoring and prognostication of various tumors. However, the specific roles and molecular mechanisms of action of THBS1 in ATC remain unclear. In this study, we found that Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA), a THBS1 inhibitor, significantly inhibited ATC tumor growth both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, we demonstrated that <em>THBS1</em> was the target gene of PA-MSHA in ATC and identified the THBS1/FAK/AKT axis as the key antitumor signaling pathway. Furthermore, we confirmed that THBS1 was overexpressed in ATC tumors and that high levels of THBS1 were associated with a poorer prognosis in thyroid cancer. Silencing <em>THBS1</em> significantly decreased p-FAK and p-AKT levels, resulting in significant inhibition of cell proliferation and apoptosis in ATC cells. These findings suggest that the THBS1/FAK/AKT axis is a promising therapeutic target for ATC treatment.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114373"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of cancer cell-derived exosomal proteins on macrophage polarization: An in-depth review","authors":"Khandu Wadhonkar ,&nbsp;Soumalya Das ,&nbsp;Ramachandran Subramanian ,&nbsp;Mobbassar Hassan Sk ,&nbsp;Yashi Singh ,&nbsp;Mirza S. Baig","doi":"10.1016/j.yexcr.2024.114393","DOIUrl":"10.1016/j.yexcr.2024.114393","url":null,"abstract":"<div><div>Cancer is characterized by unregulated cell proliferation, enabling it to invade and spread to different organs and tissues in the body. Cancer progression is intricately influenced by the complex dynamics within the tumor microenvironment (TME). The TME is a composite and dynamic network comprising cancer cells and various immune cells, including tumor-associated macrophages. Exosomes facilitate the communication between different cancer cells as well as other types of cells. This review particularly focuses on exosomal proteins derived from different cancer cells in mounting the complex crosstalk between cells of cancer and macrophages within the TME. Most cancer-derived exosomal proteins polarize macrophages towards M2 phenotype, promoting cancer aggressiveness, while a few have role switching towards the M1 phenotype, inhibiting cancer proliferation, respectively. In this review, we summarize, for the first time, the dual impact of cancer cell-derived exosomal proteins on macrophage polarization and the associated signaling pathways, offering valuable insights for developing innovative therapeutic strategies against diverse cancer types.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114393"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEMA3C promotes thyroid cancer via the Wnt/β-catenin pathway","authors":"Shiwei Li ,&nbsp;Yanmei Cheng ,&nbsp;Changhui Gao ,&nbsp;Qingling Yuan ,&nbsp;Xiubo Lu","doi":"10.1016/j.yexcr.2024.114378","DOIUrl":"10.1016/j.yexcr.2024.114378","url":null,"abstract":"<div><div>Semaphorin 3C (SEMA3C) regulates the progression of several tumors. However, the role of SEMA3C in thyroid cancer remains unknow. In the present study, SEMA3C was overexpressed or knocked down in thyroid cancer cell lines BCPAP and IHH-4. It was found that SEMA3C promoted the cell migration, invasion, and mesenchymal–epithelial transition (EMT) process. SEMA3C overexpression enhanced tumor cell stemness, while SEMA3C knockdown showed the opposite effects. In vivo experiments suggested that SEMA3C accelerated the tumor growth and metastasis. Moreover, SEMA3C enhanced β-catenin nuclear translocation. When cells were treated with Dickkopf-1 (DKK1), an inhibitor of Wnt/β-catenin pathway, the promoting effects of SEMA3C on cell migration and stemness were offset. Wnt/β-catenin pathway mediated the roles of SEMA3C in thyroid cancer. Additionally, an upstream regulator of SEMA3C was identified. E1A binding protein P300 (P300) was found to increase the histone three lysine 27 acetylation (H3K27ac) level of SEMA3C, promoting its transcriptional activation. Therefore, we clarify that SEMA3C exerts a tumor-promoting effect on thyroid cancer, and Wnt/β-catenin pathway is the critical downstream pathway.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114378"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes derived from cardiac fibroblasts with Ang-II stimulation provoke myocardial hypertrophy via miR-15b-5p/PTEN-L axis","authors":"Zhiwen Hu ,&nbsp;Dijiu Xiao ,&nbsp;Liang Wang ,&nbsp;Jiaxiang You ,&nbsp;Tao Long ,&nbsp;Jinping Wang ,&nbsp;Yibiao Shang ,&nbsp;Dasong Yi ,&nbsp;Lu Ding ,&nbsp;Xiang Wang ,&nbsp;Xiaoping Peng ,&nbsp;Junyi Zeng","doi":"10.1016/j.yexcr.2024.114380","DOIUrl":"10.1016/j.yexcr.2024.114380","url":null,"abstract":"<div><div>This study aimed to examine the impact of exosomes derived from Ang II-stimulated cardiac fibroblasts (CFs) on myocardial hypertrophy. Neonatal rat CFs were isolated and identified using Vimentin immunofluorescence. Following Ang II stimulation, exosomes were collected, characterized, and subjected to miRNA sequencing. Myocardial hypertrophy models were induced both <em>in vitro</em> and <em>in vivo</em> using Ang II. CFs were transfected with miR-15b-5p mimics or inhibitors, and their exosomes were co-cultured with rat cardiomyocytes (H9C2). Changes in cell viability, myocardial hypertrophy, and the expression levels of PTEN-L, PINK1, and Parkin proteins were assessed using the CCK-8 assay, cell surface area evaluation, and Western blot analysis. Cardiac tissue pathology and myocardial hypertrophy were evaluated through HE and WAG staining, respectively, while PTEN-L expression was detected by immunohistochemistry. The results demonstrated successful isolation of CFs and their exosomes, with miR-15b-5p significantly enriched in the exosomes derived from Ang II-stimulated CFs (Ang II-CFs-Exos). Ang II-CFs-Exos inhibited cell viability, exacerbated myocardial hypertrophy, and activated mitophagy via miR-15b-5p in the <em>in vitro</em> myocardial hypertrophy model. PTEN-L was identified as a downstream target of miR-15b-5p, with its overexpression reversed the effects of miR-15b-5p mimic on myocardial hypertrophy and mitophagy. Additionally, mitochondrial inhibitors also countered the effects of the miR-15b-5p mimic on myocardial hypertrophy. Furthermore, Ang II-CFs-Exos exacerbated myocardial hypertrophy in rats, while knockout of miR-15b-5p in Ang II-CFs-Exos mitigated this effect. To sum up, Ang II-CFs-Exos promote myocardial hypertrophy by modulating PINK1/Parkin signaling -mediated mitophagy through the miR-15b-5p/PTEN-L axis.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114380"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AZD1390, an Ataxia telangiectasia mutated inhibitor, enhances cisplatin mediated apoptosis in breast cancer cells","authors":"Deniz Özdemir,&nbsp;Can Ali Ağca","doi":"10.1016/j.yexcr.2024.114382","DOIUrl":"10.1016/j.yexcr.2024.114382","url":null,"abstract":"<div><div>Genomic instability is often caused by deficiencies in DNA damage repair pathways, making therapeutic targeting of DDR beneficial for cancer patients with specific DDR functions. ATM kinase plays a critical role in various cellular processes and its deficiency increases sensitivity to DDR-targeted agents in different cancers. Recent studies highlight ATM inhibition as a potential clinical target, with AZD1390 being a notable ATM inhibitor due to its potent and selective inhibition, ability to accumulate at DNA breaks. The study aimed to evaluate the potential anti-cancer effects of AZD1390, a key component of the DNA damage response, in breast cancer cells. The impact of the combination of AZD1390 and cisplatin on various parameters such as cell viability, proliferation, colony formation capacity, DNA damage, reactive oxygen species (ROS) levels, mitochondrial membrane potential, cell cycle progression, and cell death in breast cancer cells was evaluated using several methodologies, including WST-1 assays, real-time cell analysis, colony formation assays, comet assays, DCF-DA, MMP/JC-1 staining assays, flow cytometry along with Western blot analysis. We found that AZD1390 and cisplatin displayed synergistic antitumor effects in breast cancer cells at low doses. Addinationaly exhibited significant anti-proliferative effects in colony formation and real-time cell proliferation experiments, increasing intracellular ROS levels and mitochondrial membrane potential.The combined treatment also arrested the cell cycle at the G2-M point. Furthermore, combination of AZD1390 with cisplatin enhances its apoptotic effects in MCF-7 and MDA-MB-231 cells. These findings could aid in developing new treatments for breast cancer that exploit the genomic instability of cancer cells.</div></div>","PeriodicalId":12227,"journal":{"name":"Experimental cell research","volume":"444 2","pages":"Article 114382"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}