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Preliminary Insights Into the Combined Antitumor Efficacy of Onco-VV-TT and Natural Killer Cells in Glioblastoma Onco-VV-TT与自然杀伤细胞联合抗胶质母细胞瘤疗效的初步观察
IF 3.1 3区 生物学
Cell Biology International Pub Date : 2026-06-12 DOI: 10.1002/cbin.70176
Seyedeh Nasim Mirbahari, Davood Sanooghi, Marzieh Ebrahimi, Hamid Mahdizadeh, Ali Davari, Amir-Abbas Hedayati Asl, Sahel Ahmadpour Torkamani, Mahdi Hesaraki, Mehdi Totonchi
{"title":"Preliminary Insights Into the Combined Antitumor Efficacy of Onco-VV-TT and Natural Killer Cells in Glioblastoma","authors":"Seyedeh Nasim Mirbahari,&nbsp;Davood Sanooghi,&nbsp;Marzieh Ebrahimi,&nbsp;Hamid Mahdizadeh,&nbsp;Ali Davari,&nbsp;Amir-Abbas Hedayati Asl,&nbsp;Sahel Ahmadpour Torkamani,&nbsp;Mahdi Hesaraki,&nbsp;Mehdi Totonchi","doi":"10.1002/cbin.70176","DOIUrl":"10.1002/cbin.70176","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates the therapeutic efficacy and safety of Onco-VV-TT, a genetically engineered oncolytic vaccinia virus, in the treatment of glioblastoma (GBM), with and without the combination of natural killer (NK) cell immunotherapy. A comprehensive set of in vitro and in vivo experiments was conducted to assess viral cytotoxicity, replication, tumor penetration, and immunomodulatory effects. Onco-VV-TT selectively reduced the viability of GBM cell lines (U251, U87, and C6) in a time- and dose-dependent manner while sparing normal fibroblasts. The virus significantly impaired clonogenicity, migration, and stemness-related gene expression in U251 cells. Confocal imaging confirmed viral replication and deep penetration into 3D spheroids. NK cells demonstrated strong cytotoxicity against U251 cells in both 2D and 3D models. In a xenograft mouse model, intratumoral administration of Onco-VV-TT suppressed tumor growth and significantly prolonged survival; NK cell monotherapy showed limited efficacy, while the addition of NK cells further enhanced therapeutic outcomes. Immunological analyses revealed that combination therapy elevated pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-6) and increased WBC count, reflecting an expected transient systemic inflammatory response to vaccinia virus exposure rather than a direct enhancement of antitumor immunity. Histopathological and immunohistochemical analysis showed reduced mitosis, increased apoptosis, decreased cancer stem cell marker CD133, and lower VEGF expression in tumors treated with Onco-VV-TT and NK cells. Safety evaluations in immunocompetent mice demonstrated no significant systemic toxicity or organ damage following intravenous injection of Onco-VV-TT. Transient inflammatory marker elevation resolved by day 21, and all hematological and biochemical parameters remained within normal range. These findings suggest that Onco-VV-TT, particularly in combination with NK cell therapy, is a promising and well-tolerated approach for GBM treatment, meriting further preclinical and clinical development.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223743","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}
引用次数: 0
Chemical Reprogramming of Fibroblasts to Functional Mammary Epithelial Cells via a Single BMP Inhibitor 通过单一BMP抑制剂化学重编程成纤维细胞到功能性乳腺上皮细胞。
IF 3.1 3区 生物学
Cell Biology International Pub Date : 2026-06-05 DOI: 10.1002/cbin.70173
Quanhui Liu, Dandan Zhang, Guodong Wang, Zhigang Lei, Shan Deng, Lianggui Xiao, Mengqin Qin, Ben Huang
{"title":"Chemical Reprogramming of Fibroblasts to Functional Mammary Epithelial Cells via a Single BMP Inhibitor","authors":"Quanhui Liu,&nbsp;Dandan Zhang,&nbsp;Guodong Wang,&nbsp;Zhigang Lei,&nbsp;Shan Deng,&nbsp;Lianggui Xiao,&nbsp;Mengqin Qin,&nbsp;Ben Huang","doi":"10.1002/cbin.70173","DOIUrl":"10.1002/cbin.70173","url":null,"abstract":"<div>\u0000 \u0000 <p>Direct lineage reprogramming offers a highly promising non-genetic pathway for generating functional somatic cells. In this study, a single small molecule inhibitor of the BMP pathway, LDN193189, was able to directly reprogram goat ear fibroblasts into Chemically induced Mammary Epithelial Cells (CiMECs) in vitro within 8 days. The generated CiMECs displayed typical epithelial morphology, expressed key mammary epithelial markers (including KRT8/14/18/19, CD49f, and EpCAM), and exhibited potent secretory functions: they could form lipid droplets and produce milk proteins such as lactoferrin (LTF) and αS2-casein (αS2-CSN). Single-cell RNA sequencing revealed a stepwise reprogramming trajectory: starting from mesenchymal–epithelial transition (MET), through ectoderm-like and epidermal-like intermediate states to differentiate into basal and lumenal mammary epithelial cells, which involves multiple signaling pathways related to mammary gland development, such as TGF-β, MAPK, and PI3K-Akt. Functionally, CiMECs could self-assemble in vitro to form three-dimensional mammary-like organs. In addition, in vivo transplantation experiments in nude mice showed that these CiMECs survived and contributed to ductal- and basal-like tissue structures, confirming their in vivo regenerative potential. In conclusion, this study establishes a simple somatic cell-based platform with a well-defined chemical composition to efficiently generate functional mammary epithelial cells, providing an important model for mammary developmental studies and opening up promising strategies for regenerative medicine and bioreactor engineering applications.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148162032","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}
引用次数: 0
Vitamin B6 Ameliorates Lipopolysaccharide-Induced Inflammation in Mouse Gastric Organoids 维生素B6改善小鼠胃类器官脂多糖诱导的炎症。
IF 3.1 3区 生物学
Cell Biology International Pub Date : 2026-06-02 DOI: 10.1002/cbin.70172
Aoqing Xu, Yijin Wu, Xiyu Wang, Jiaming Wang, Fengrui Yang, Xia Ding, Chuanhai Fu, Yuxing Chen, Ze-Xian Liu, Zhikai Wang, Xing Liu
{"title":"Vitamin B6 Ameliorates Lipopolysaccharide-Induced Inflammation in Mouse Gastric Organoids","authors":"Aoqing Xu,&nbsp;Yijin Wu,&nbsp;Xiyu Wang,&nbsp;Jiaming Wang,&nbsp;Fengrui Yang,&nbsp;Xia Ding,&nbsp;Chuanhai Fu,&nbsp;Yuxing Chen,&nbsp;Ze-Xian Liu,&nbsp;Zhikai Wang,&nbsp;Xing Liu","doi":"10.1002/cbin.70172","DOIUrl":"10.1002/cbin.70172","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric mucosal inflammation is a critical precondition of various gastric diseases, and development of safe and effective anti-inflammatory agents for prompt resolution of acute inflammation at early stage is vital to preventive medicine. B vitamins are essential water-soluble nutrients with reported anti-inflammatory properties, yet their potent regulatory effects in gastric mucosal inflammation are not systemically assessed. In this study, we adopted a lipopolysaccharide (LPS)-induced inflammatory mouse gastric organoid model to screen for anti-inflammatory B vitamin family members. With the anti-inflammatory effect of vitamin B12 (VB12) being validated in this gastric organoid model, which is consistent with the roles in other biological settings, further screening of the rest B vitamin members identified vitamin B6 (VB6) as the most potent anti-inflammatory agent as it preventatively ameliorated LPS-induced organoid collapse and preserved gastric epithelial polarity in the inflammatory organoids. Functional assays confirmed that VB6 significantly downregulated the expressions of key pro-inflammatory <i>Tnf</i>, <i>Cxcl1</i>, and <i>Il1b</i> genes, and inhibited TNF-α and IL-1β protein secretions. Further mechanistic exploration revealed that VB6 antagonized LPS-induced inflammatory responses by targeting the transcription of positive regulatory genes in core LPS-mediated inflammatory signaling pathways. These findings provide important experimental evidence for the development of nutrition-based intervention strategies for gastric inflammatory diseases in human.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142896","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}
引用次数: 0
Establishment and Molecular Characterization of a Short-Term Primary Culture Derived From Invasive Micropapillary Carcinoma of the Breast. 浸润性乳腺微乳头状癌短期原代培养物的建立及分子表征。
IF 3.5 3区 生物学
Cell Biology International Pub Date : 2026-06-01 DOI: 10.1002/cbin.70167
Mamta Gurav, Omshree Shetty, Shalaka Joshi, Seema Gulia, Rohan Chaubal, Sudeep Gupta, Tanuja Shet
{"title":"Establishment and Molecular Characterization of a Short-Term Primary Culture Derived From Invasive Micropapillary Carcinoma of the Breast.","authors":"Mamta Gurav, Omshree Shetty, Shalaka Joshi, Seema Gulia, Rohan Chaubal, Sudeep Gupta, Tanuja Shet","doi":"10.1002/cbin.70167","DOIUrl":"10.1002/cbin.70167","url":null,"abstract":"<p><p>Invasive micropapillary carcinoma (IMPC) of the breast, a rare and aggressive subtype, represents a unique morphology of reversed polarity with higher metastatic propensity. Due to the limited availability of experimental models, understanding distinct molecular pathways and potential therapeutic targets remains challenging. This study aimed to establish patient-derived cell cultures (PDCs) from IMPC to generate viable models for in-vitro studies. Tissue samples from five IMPC cases were enzymatically disaggregated using five different cell disaggregation protocols. These cells were characterized using immunofluorescence, short tandem repeats profiling, and real-time assays for tumor marker expression profiles. RNA sequencing was performed and compared with invasive ductal carcinoma, no special type (IDC-NST), to study differential gene expression and cell polarity markers. Two short-term PDCs were successfully established from IMPC samples with an optimized collagenase-based protocol. These cultures showed an immunohistochemical profile consistent with the original tumor tissues and maintained hormone receptor and MUC1 expression status. RNA sequencing of PDCs revealed similar gene expression patterns with matched tumor tissue and revealed upregulated RAP1, MAPK, and PI3K-AKT pathways, when compared with ER/PR-matched IDC. These PDCs also showed different gene expression patterns in cell-polarity associated genes, such as cadherins CDH2, tight junction gene MARVELD2, PAR complex gene PARD6B, and downregulation of the cell polarity CRB2 gene. This study indicated the need for an optimization of cell culture conditions and the feasibility of establishing patient-derived cell cultures from IMPC. These models provide a great tool to study molecular insights, cell polarity, and therapeutic research in a rare breast cancer subtype.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":"e70167"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004823","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}
引用次数: 0
Picrosides I and II Ameliorate Steatosis by Modulating Lipogenesis, Mitochondrial Biogenesis, and Autophagy in Hepatic Cells. Picrosides I和II通过调节脂肪生成、线粒体生物发生和肝细胞自噬改善脂肪变性。
IF 3.5 3区 生物学
Cell Biology International Pub Date : 2026-06-01 DOI: 10.1002/cbin.70170
Swati Katoch, Jatin, Vishal Acharya, Vikram Patial
{"title":"Picrosides I and II Ameliorate Steatosis by Modulating Lipogenesis, Mitochondrial Biogenesis, and Autophagy in Hepatic Cells.","authors":"Swati Katoch, Jatin, Vishal Acharya, Vikram Patial","doi":"10.1002/cbin.70170","DOIUrl":"10.1002/cbin.70170","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is marked by excessive fat accumulation in the hepatocytes. In the present study, the protective efficacy of picroside I and II against steatosis was studied using combination of in silico and in vitro approaches. The in silico studies revealed moderate to high binding affinity of the picroside I and II with the various proteins involved in mitochondrial biogenesis and autophagy. Further, picrosides I and II treatment significantly reduced the lipid accumulation and triglyceride levels in the palmitate-oleate (PO)-treated Huh7 cells. Picrosides significantly downregulated various lipogenic markers (SREBP1c, ChREBP, SCD1, and FAS) and upregulated AMPKα. The PO treatment elevated ROS production and lipid peroxidation (MDA) in the hepatic cells, which was significantly lowered by picrosides. PO treatment also led to mitochondrial dysfunction; however, picrosides significantly restored mitochondrial function by improving mitochondrial membrane potential (MMP), mitochondrial DNA levels and upregulating the mitochondrial biogenesis (PGC1α, TFAM, NRF1 and NRF2). Further, picrosides lowered the levels of inflammatory cytokines (TNF-α, IL6 and IL1β) and expressions of NFκB in the PO-treated Huh7 cells. PO treatment impaired the autophagy by altering the expressions of autophagy markers (SQSTM1, BECN1, MAPLC3A, ATG5, and ATG7) in the PO-treated Huh7 cells. Picroside treatment improved the autophagic flux by modulating the expressions of various autophagy biomarkers. In conclusion, the picroside I and II effectively prevented the steatohepatitis by lowering the lipogenesis, oxidative stress and inflammation, which improved the mitochondrial biogenesis and autophagic reflux in the hepatic cells.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":"e70170"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027678","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}
引用次数: 0
Ganodermanontriol and Lanostane Triterpenoid Derivatives in Cancer Cell Biology: Signaling Network Modulation, Cell-Cycle Control and Tumor Microenvironment Reprogramming. 肿瘤细胞生物学中的灵芝皂苷三醇和毛甾烷三萜衍生物:信号网络调节、细胞周期控制和肿瘤微环境重编程。
IF 3.5 3区 生物学
Cell Biology International Pub Date : 2026-06-01 DOI: 10.1002/cbin.70166
Robert Kubina, Maria-Laura Morawiec, Ilona Nowak, Robert Sarna, Kamil Krzykawski, Agata Kabała-Dzik, Arkadiusz Dziedzic, Aleksandra Mielczarek-Palacz, Javad Sharifi-Rad, William N Setzer, Daniela Calina
{"title":"Ganodermanontriol and Lanostane Triterpenoid Derivatives in Cancer Cell Biology: Signaling Network Modulation, Cell-Cycle Control and Tumor Microenvironment Reprogramming.","authors":"Robert Kubina, Maria-Laura Morawiec, Ilona Nowak, Robert Sarna, Kamil Krzykawski, Agata Kabała-Dzik, Arkadiusz Dziedzic, Aleksandra Mielczarek-Palacz, Javad Sharifi-Rad, William N Setzer, Daniela Calina","doi":"10.1002/cbin.70166","DOIUrl":"10.1002/cbin.70166","url":null,"abstract":"<p><p>Ganodermanontriol (GDNT), a lanostane-type triterpenoid derived from Ganoderma lucidum, exhibits multiple pharmacological properties, with emerging evidence supporting its anticancer potential. Despite the long-standing medicinal use of G. lucidum, the specific role and mechanisms of GDNT in oncology require further clarification. This review presents a comprehensive analysis of preclinical studies investigating the anticancer activity of GDNT in various cancer types, including nasopharyngeal, hepatocellular, gastric, colorectal, breast, prostate, and lung malignancies. Relevant experimental literature was identified and evaluated, with emphasis on in vitro and in vivo models exploring the molecular mechanisms of GDNT. Key pathways implicated in its activity include NF-κB/MAPK, TLR4/MyD88, Wnt/β-catenin, CES2/MPA metabolism, and androgen receptor signaling. Experimental findings demonstrate that GDNT induces apoptosis, arrests cell cycle progression, and inhibits tumor cell proliferation, migration, and invasion. It also modulates the tumor microenvironment through suppression of M2 macrophage polarization and pro-tumor cytokine expression. Semi-synthetic analogs of GDNT display improved cytotoxicity and selectivity, highlighting the relevance of structural optimization in enhancing bioactivity. Although clinical data on GDNT are currently lacking, studies involving G. lucidum extracts suggest potential benefits as supportive agents in oncologic care, particularly in immune modulation and enhancement of chemotherapeutic efficacy. Ongoing research into GDNT's pharmacological profile, including its derivatives, may support its development as a novel candidate in cancer therapeutics.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":"e70166"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970728","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}
引用次数: 0
Berberine Chloride Induces Apoptosis and Inhibits Adhesion, Migration, and Invasion in MDA-MB-231 and 4T1 Breast Cancer Cells: An Integrative In Vitro and In Silico Study. 氯化小檗碱诱导MDA-MB-231和4T1乳腺癌细胞凋亡并抑制粘附、迁移和侵袭:一项体外和计算机综合研究
IF 3.5 3区 生物学
Cell Biology International Pub Date : 2026-06-01 DOI: 10.1002/cbin.70165
Abir Salek, Mouna Selmi, Aida Lahmer, Mabrouk Horchani, Mouna Maatouk, Mahassen Barboura, Haifa Messai, Jihed Boubabaker, Hichem Ben Jannet, Leila Chekir-Ghedira, Ines Bouhlel-Chatti
{"title":"Berberine Chloride Induces Apoptosis and Inhibits Adhesion, Migration, and Invasion in MDA-MB-231 and 4T1 Breast Cancer Cells: An Integrative In Vitro and In Silico Study.","authors":"Abir Salek, Mouna Selmi, Aida Lahmer, Mabrouk Horchani, Mouna Maatouk, Mahassen Barboura, Haifa Messai, Jihed Boubabaker, Hichem Ben Jannet, Leila Chekir-Ghedira, Ines Bouhlel-Chatti","doi":"10.1002/cbin.70165","DOIUrl":"10.1002/cbin.70165","url":null,"abstract":"<p><p>Berberine chloride (BRB), an isoquinoline alkaloid isolated from Berberis vulgaris, demonstrated significant anticancer activity against breast cancer. This study assessed the therapeutic effects of BRB on cell proliferation, cell-cycle progression, apoptosis, and metastasis in human (MDA-MB-231) and murine (4T1) triple-negative breast cancer cells. Cytotoxicity testing using a crystal violet assay showed IC₅₀ values of 40 µM for MDA-MB-231 and 10 µM for 4T1 after 48 h of treatment. BRB induced S-phase arrest in MDA-MB-231 and G2/M-phase arrest in 4T1 cells. It also induced late apoptosis in both cell lines, along with increased reactive oxygen species production and loss of mitochondrial membrane potential. Furthermore, BRB exhibited marked anti-metastatic potential by inhibiting cell adhesion, migration, and invasion. Scratch-wound and Transwell assays demonstrated a significant, concentration-dependent reduction in migratory capacity, while 3D spheroid assays confirmed strong suppression of invasive behavior. BRB also reduced adhesion to extracellular matrix components, particularly collagen IV. At the molecular level, BRB significantly downregulated MMP2 and MMP9 mRNA expression in both cell lines, supporting its role in inhibiting extracellular matrix remodeling and metastatic progression. Molecular docking simulations indicated that BRB has a favorable binding energy with multiple cancer-related targets, including MDM2-P53, BCL2, Caspases (3, 8, and 9), MCL1 complexes, and matrix metalloproteinases (MMP-2 and MMP-9). The compound maintained stable hydrogen bonds, ππ-stacking interactions, and hydrophobic contacts, often achieving higher docking scores than the co-crystallized ligand. Overall, the results suggest that BRB exerts multi-targeted anticancer effects by regulating processes such as proliferation, apoptosis, migration, and adhesion, indicating that BRB could be a promising candidate for breast cancer therapy.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":"e70165"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970794","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}
引用次数: 0
Tamoxifen Modulates Actin Stress Fibre Dynamics Through c-Src-MLCK Signalling in Breast Cancer Cells. 他莫昔芬通过乳腺癌细胞c-Src-MLCK信号调节肌动蛋白应激纤维动态。
IF 3.5 3区 生物学
Cell Biology International Pub Date : 2026-06-01 DOI: 10.1002/cbin.70169
Bidisha Biswas, Shahnawaz Ahmed, Sowmya Manickavasagan, Akshay Jitendra Chaudhari, Sudhagar Selvaraju
{"title":"Tamoxifen Modulates Actin Stress Fibre Dynamics Through c-Src-MLCK Signalling in Breast Cancer Cells.","authors":"Bidisha Biswas, Shahnawaz Ahmed, Sowmya Manickavasagan, Akshay Jitendra Chaudhari, Sudhagar Selvaraju","doi":"10.1002/cbin.70169","DOIUrl":"10.1002/cbin.70169","url":null,"abstract":"<p><p>Emerging evidence suggests that cytoskeletal dynamics are critical in drug resistance and metastasis. The present study investigates the influence of tamoxifen on actin stress fibre organisation in breast cancer cells. We demonstrate that tamoxifen treatment induces significant morphological changes, including increased cell spreading and polarity and enhanced migratory potential in breast cancer cells T47D and ZR-75-1. A loss of organised actin stress fibres and the emergence of lamellipodia and filopodia by tamoxifen treatment indicate its direct role in actin cytoskeleton remodelling, which was further confirmed by western blot analyses of key actin regulators. Upstream tamoxifen activates c-Src kinase, while reducing phosphorylation of myosin light chain (MLC), a key stress fibre regulator that activates myosin II. Further, inhibition of c-Src kinase with PP2 or silencing using siRNA reversed tamoxifen-induced stress fibre loss, confirming c-Src's pivotal role in modulating actin dynamics. These findings highlight a novel mechanism by which tamoxifen influences breast cancer cell actin dynamics and motility.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":"e70169"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027612","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}
引用次数: 0
Cell Line-Specific In Vitro Effects of Boric Acid and Meis1i-2 in Leukemia Cells: Apoptosis, Cell-Cycle Modulation, and Fixed-Dose Interaction 硼酸和meis1 -2在白血病细胞中的体外作用:凋亡、细胞周期调节和固定剂量相互作用。
IF 3.1 3区 生物学
Cell Biology International Pub Date : 2026-06-01 DOI: 10.1002/cbin.70171
Neslihan Meriç, Aynura Mammadova, Fatih Kocabaş, Fatih Kar
{"title":"Cell Line-Specific In Vitro Effects of Boric Acid and Meis1i-2 in Leukemia Cells: Apoptosis, Cell-Cycle Modulation, and Fixed-Dose Interaction","authors":"Neslihan Meriç,&nbsp;Aynura Mammadova,&nbsp;Fatih Kocabaş,&nbsp;Fatih Kar","doi":"10.1002/cbin.70171","DOIUrl":"10.1002/cbin.70171","url":null,"abstract":"<div>\u0000 \u0000 <p>Leukemia, a hematological malignancy resulting from genetic mutations and environmental factors, leads to uncontrolled proliferation and impaired differentiation of hematopoietic cells. Current treatment modalities face limitations such as drug resistance and off-target toxicity, highlighting the need for novel therapeutic strategies. This study evaluates the individual and fixed-dose combined in vitro effects of boric acid (BA) and Myeloid Ecotropic Viral Integration Site 1 Inhibitor-2 (Meis1i-2) in leukemia cell lines, focusing on apoptosis, cell-cycle distribution, and selected transcript-level changes. Three distinct leukemia cell lines (K562, RS4-11, CCRF-CEM) were cultured under standardized conditions and treated with varying concentrations of BA and Meis1i-2 individually and in combination. Apoptotic cell death was evaluated using flow cytometry-based Annexin V–FITC/PI staining, while cell cycle dynamics were assessed via Hoechst 33342 and Pyronin Y staining followed by flow cytometric analysis. Additionally, quantitative RT-PCR (qRT-PCR) was employed to determine the expression levels of apoptosis-related and cell cycle regulatory genes. At the 72-h endpoint, BA and Meis1i-2 produced measurable changes in viability, apoptosis, and cell-cycle distribution in a cell-line- and concentration-dependent manner. The high-dose fixed combination of BA (2000 µM) and Meis1i-2 (10 µM) reduced viability compared with DMSO controls in several assays; however, this condition was above the RS4-11 IC<sub>50</sub> values and should be interpreted as a supra-IC<sub>50</sub> exploratory condition rather than evidence of superiority over the most active single agent. Annexin V/PI and cell-cycle analyses showed treatment-associated apoptotic changes and redistribution of G1, S, and G2/M phases depending on the cell line. Targeted qRT-PCR indicated transcript-level modulation of selected apoptosis- and cell-cycle-related genes, but these changes were not uniform across all models. These findings reveal that BA and Meis1i-2 exhibit biologically measurable antileukemic effects through apoptosis induction and cell cycle modulation. However, Chou-Talalay analysis in RS4-11 cells yielded CI values greater than 1 at the tested concentrations, suggesting an antagonistic rather than non-synergistic under the tested conditions. Therefore, under the current experimental conditions, the combination demonstrates concentration-specific antileukemic activity rather than pharmacological interaction. Future studies using expanded sub-IC<sub>50</sub> dose matrices, protein-level and functional validation, and in vivo models are required.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136764","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}
引用次数: 0
IF 3.1 3区 生物学
Cell Biology International Pub Date : 2026-05-27
{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"50 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097493","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}
引用次数: 0
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