Nectin-4, Bladder Cancer, and Nuclear Medicine: A Theranostic Frontier.

Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function.

Nectins: Orchestrating tumor progression and immune evasion.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, and neuroinflammation. Synaptic plasticity and neuroinflammation are hallmarks of AD, with their dysregulation forming a self-reinforcing cycle that aggravates neurodegeneration. Proinflammatory cytokines impair synaptic signaling by suppressing brain-derived neurotrophic factor (BDNF) expression and neuroplasticity markers, further compromising synaptic plasticity. β-Caryophyllene (BCP), a natural bicyclic sesquiterpene with anti-inflammatory and neuroprotective properties, may counteract these pathological processes. This study evaluated the effect of BCP in mitigating streptozotocin (STZ)-induced AD-like conditions in male Sprague-Dawley rats. Two doses of STZ (3 mg/kg) on Days 1 and 3 were administered intracerebroventricularly to induce AD-like pathology. Rats received BCP (10, 20 mg/kg, i.p.) or rivastigmine (2.5 mg/kg) for 28 days. Cognitive performance was assessed using the Barnes maze and novel object recognition tests. Hippocampal tissues were analyzed for BDNF expression, synaptic plasticity markers (e.g., synaptophysin, neural cell adhesion molecule [NCAM], and ciliary neurotrophic factor [CNTF]), neuroinflammatory markers (e.g., IL-1β, TNF-α, IL-6, COX2, and NF-κB), and oxidative stress markers. Histological (hematoxylin and eosin) and Golgi-Cox staining techniques were employed to evaluate neuronal integrity and synaptic organization. STZ-induced rats exhibited significant cognitive deficits, synaptic loss, and increased neuroinflammation. BCP treatment improved spatial learning and memory retention, increased BDNF expression, and restored synaptic plasticity markers. Furthermore, BCP attenuated neuroinflammation by reducing proinflammatory cytokine levels. Histopathology confirms normal hippocampal neuronal architecture in BCP-treated groups. These findings highlight the ability of BCP to modulate BDNF signaling, synaptic plasticity, and neuroinflammatory pathways, underscoring its potential as a multitarget therapeutic candidate for AD.

Exploration of the hemocyte surfaceome of Apis mellifera by a proteomic and transcriptomic approach.

Abstract Background Lupus Nephritis (LN) is one of the most common and serious manifestations which occur in 50-80% of pediatric systemic lupus erythromatosis (SLE) patients. Urinary activated leukocyte cell adhesion molecule (ALCAM) is a potential non-invasive biomarker that may predict renal pathology activity index in LN and may serve as a valuable surrogate marker of renal histopathology. We aimed at evaluating the role of urinary ALCAM as a diagnostic biomarker in LN and its relation to the disease activity and histopathological severity. Methods This study was a cross-sectional study, where we included pediatric SLE patients from 6 to 18 years, who follow up regularly at Pediatric Allergy, Immunology and Rheumatology clinic, Children’s Hospital, Ain Shams University, and similar number of age and gender matched controls. Patients were divided into two equal groups; group 1: SLE LN, group 2: SLE Non-LN. Clinico-demographics, and laboratory data were collected and analyzed to assess disease activity by total and renal SLEDAI score, also, renal biopsy results for LN. Urinary ALCAM levels were measured using ELISA, and correlated to disease activity and histopathology severity. Results We included 60 SLE patients (30 patients with LN and 30 non- LN), and 60 controls with mean±SD age of 12.38±2.35, and 13.4±2.43 years (p > 0.05) respectively. The mean±SD SLE duration and SLEDAI score of all SLE patients (10 days before enrolment) was 18.19±18.97 months and11.3±3 respectively. In LN group, the median renal SLEDAI (IQR) was 6.5 (2.4), and class II (40%) was the most common class with median (IQR) chronicity and activity indices of 2 (IQR1-3), and 5.5 (IQR2-9) respectively. The median (IQR) urinary ALCAM levels were significantly higher in LN group than non- LN group and controls [1001.6 (766.4 - 1186) vs 229.7 (182 - 270.5), 209.7 (150 - 250.5) ng/mL respectively] (p < 0.001).Urinary ALCAM was positively correlated with 24-hour urinary proteins, and renal SLEDAI score (p < 0.005), meanwhile it showed no statistically significant correlation with LN class, activity and chronicity indices. Conclusion Urinary ALCAM levels were significantly higher in LN patients compared to non-LN SLE patients and healthy controls, indicating its potential role in LN detection. Additionally, it correlated positively with proteinuria and renal SLEDAI scores, suggesting its association with disease activity. Meanwhile, it reflects renal inflammation, but it does not necessarily predict histological severity.

Multiple sclerosis is a complex autoimmune disorder of the central nervous system and is believed to be caused by dysfun c tion of the immune system, characterized by inflammatory demyelination with axonal transection. Sixty blood samples were collected from patients (25 females and 35 males) suffering from multiple sclerosis (MS) who visited the MS consultant at Bag h dad Teaching Hospital, affiliated to the Medical City. Patients were collected from different age groups ranging from 20 – 40 years. Forty samples (15 females and 25 males) were collected from healthy individuals as a control group. Several biochem i cal parameters were tested, such as v imentin, neural cell adhesion molecule-NCAM, C-X-C motif chemokine ligand 10 ( CXCL10 ) , toll -like receptor 4 ( TLR4 ) , magnesium , zinc in the patients ’ blood serum. The results of the current study indicated a significant increase in v imentin, NCAM, CXCL10, TLR4 concentration in the blood serum of the G1 group compared to the control group. Also, the result showed a significant low in Mg, Zn concentration in the blood serum of the G1 group compared to the control group. The results also showed a highly significant positive correlation between vimentin concentration and NCAM, TLR4, CXCL10, Mg, Zn in the blood serum of the healthy group, which reache d correlation coefficients was 0.557, 0.848, 0.928, 0.633, 0.640, respectively. The results also showed that the area under curve value for the studied variables was excellent, as they can be considered important diagnostic variables for patients with multiple sclerosis.

To examine the role of circulating tumor cell analysis in tailoring therapy for recurrent ovarian cancer by determining the survival outcomes of patients who received circulating tumor cell-guided therapy. A retrospective chart review of patients who received circulating tumor cell-guided therapy for recurrent epithelial ovarian cancer at a single center between September 2015 and May 2024. Of 334 records of patients reviewed, 88 patients (26.35%) were referred to circulating tumor cell testing to determine tumor response to therapy and 66 (19.76%) received circulating tumor cell-guided therapy. The median progression-free survival of patients who received circulating tumor cell-guided therapy was significantly longer compared to that of their previous treatment line: 6.70 months (95% confidence interval [CI] 5.30 to 10.80) versus 4.40 months (95% CI 3.77 to 5.83), p = .0042. Twenty-seven patients (55.1%) had a progression-free survival 2/progression-free survival 1 ratio >1.3, suggesting clinical benefit. Patients who received circulating tumor cell-guided therapy had statistically significantly longer median overall survival from circulating tumor cell testing, adjusted for age at diagnosis and stage compared to patients who underwent circulating tumor cell testing but were not treated by circulating tumor cell-guided therapy (13.83 months [95% CI 8.44 to 22.14] versus 2.04 months [95% CI 1.77 to not evaluable], p = .0001). Patients with ≤5 circulating tumor cells expressing epithelial cell adhesion molecule per mL had longer overall survival from circulating tumor cell testing compared to those with >5 epithelial cell adhesion molecule per milliliter. This retrospective real-world study suggests that circulating tumor cell-guided therapy may enable better disease management, prolonging time on therapy and predicting longer survival after testing. Studies with larger cohorts are necessary to confirm our findings.

Background/Objectives: Despite advances in targeted therapies, a substantial proportion of high-risk endometrial carcinomas (EC) do not respond to treatment and have a poor prognosis. The identification of prognostic and predictive biomarkers to improve patient stratification is therefore a clinical priority. L1 cell adhesion molecule (L1CAM) is a promising biomarker in EC; however, its soluble circulating form (sL1CAM) has been poorly investigated. This study aimed to evaluate the prognostic and predictive significance of sL1CAM in high-risk ECs. Methods: High-risk EC patients, treated with surgery and platinum-based adjuvant chemotherapy, were retrospectively enrolled. sL1CAM levels were quantified in 72 preoperative serum samples by enzyme-linked immunosorbent assay (ELISA). Results: High sL1CAM levels were associated with advanced age and non-endometrioid histology. Across the entire patient cohort, higher sL1CAM concentrations significantly correlated with worse prognosis in terms of DSS and PFS in univariate (DSS: HR = 2.22, p = 0.028; PFS: HR = 1.21, p = 0.041) and multivariate (DSS: HR = 2.13, p = 0.041; PFS: HR = 1.93, p = 0.048) analyses. Stratification by histological type revealed a significant prognostic association only in the endometrioid subgroup, both in univariate and multivariate analyses. Moreover, in this subgroup, elevated sL1CAM levels were associated with shorter time to recurrence after chemotherapy, both in univariate (PFI: HR = 2.69, p = 0.027) and multivariate (PFI: HR = 2.97, p = 0.017) analysis, and significantly predicted relapse within 6 months (OR = 7.83, p = 0.027). Conclusions: sL1CAM is associated with poor prognosis in high-risk EC and seems to be associated with platinum response in endometrioid tumors. These findings support its potential role as a biomarker to improve risk stratification, warranting validation in larger, prospective studies.

Structural interactions of ankyrin B with NrCAM and β2 spectrin

MicroRNA (miR)-425-5p is used as a molecular biomarker to identify cervical cancer (CxCa). However, few studies have examined the miR-425-5p-based modulation of the vital activities of CxCa cells. The levels of neural cell adhesion molecule 1 (NCAM1) and miR-425-5p in CxCa tissues and cells were tested using western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests. CxCa cells' malignant phenotype was examined through clone formation tests, and transwell tests. CD8+T cells were co-cultured with CxCa cells and then analyzed for apoptosis rates and the expression of activation proteins (granzyme B (GZMB) and perforin) as well as immune factors (tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)) using flow cytometry, western blot, and enzyme-linked immunosorbent assay (ELISA) methods. Finally, in nude mouse experiments, the tumor size was measured for subcutaneous tumors, and the expression of CD8+T cell-related factors was detected. The NCAM1 and miR-425-5p were down-regulated and up-regulated in CxCa tissue and cells, respectively. After silencing miR-425-5p, CxCa cells showed attenuation in vitality, clone formation rate, and their capacities to migrate, penetrate, and evade immune responses. NCAM1 was targeted and silenced by miR-425-5p. When NCAM1 was silenced, it partially counteracted miR-425-5p's inhibitory effects on the immune escape and proliferation. In nude mice, the tumor size and weight decreased after silencing miR-425-5p, and levels of CD8, IFN-γ, TNF-α, perforin, and GZMB were elevated. However, these changes were reversed when NCAM1 was silenced. In conclusion, miR-425-5p mediates the biological behavior and immune evasion of CxCa cells by regulating NCAM1.

Gene transfection techniques have potential therapeutic value in reducing the inflammatory response in atherosclerosis. Atherosclerosis is a chronic inflammatory disease. Its pathological process involves multiple types of cells and signaling pathways. In recent years, researchers have used gene transfection techniques to introduce specific genes into vascular or immune cells in order to inhibit inflammatory responses, stabilize plaques, and slow down the process of atherosclerosis. Research progress has shown that gene transfection can exert anti-inflammatory effects through various mechanisms. IL-10 transfection suppresses atherosclerosis by activating the STAT3 pathway, reducing TNF-α and IL-6 expression in macrophages. Conversely, eNOS transfection enhances nitric oxide bioavailability, inhibiting endothelial cell adhesion molecule expression (e.g., VCAM-1) and monocyte recruitment. Other studies have regulated the expression of inflammation-related genes by transfecting miRNA (tiny RNA), thus inhibiting the inflammatory response of atherosclerosis. Despite preclinical efficacy, clinical translation is hindered by suboptimal vector tropism (e.g., viral vectors exhibit off-target hepatotoxicity) and immune-mediated clearance of non-viral vectors (e.g., liposomes trigger complement activation). Long-term risks of insertional mutagenesis (retroviral vectors) and epigenetic silencing of transgenes further limit durability. This paper discusses the role and mechanism of gene transfection in reducing the inflammatory response in atherosclerosis.

Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, presents with multiple variants. This study aimed to identify potential biomarkers and therapeutic candidates for PTC through computational analyses and molecular docking. Gene expression data related to PTC were obtained from the TCGA-THCA and GEO datasets (GSE35570 and GSE33630) to identify differentially expressed genes (DEGs). Functional enrichment analysis was performed on the DEGs, followed by construction of a protein-protein interaction (PPI) network. Hub genes were identified using recursive feature elimination (RFE) and LASSO regression analyses. A nomogram incorporating these hub genes was developed, and its diagnostic performance was evaluated using receiver operating characteristic (ROC) curves. Furthermore, the relationship between hub genes and immune cell infiltration was investigated. Potential drug candidates targeting the hub genes were predicted and validated through molecular docking. Common DEGs across the three datasets were enriched in pathways such as ECM-receptor interaction, proteoglycans in cancer, and cell adhesion molecules. Significantly enriched GO terms included 'binding,' 'receptor activity,' 'integral component of membrane,' 'cytoplasm,' 'cell adhesion,' and 'immune response.' A PPI network was constructed by intersecting the common DEGs with PTC-related targets. Machine learning algorithms identified three hub genes: SRY-box transcription factor 4 (SOX4), cyclin D1 (CCND1), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1). These hub genes exhibited differential expression in PTC and were used to construct a reliable diagnostic model. Furthermore, molecular docking revealed stable binding between CCND1 and Tipifarnib, suggesting potential therapeutic relevance. While previous studies have applied bioinformatics and molecular docking in PTC research, this study uniquely integrates both approaches to identify the hub gene CCND1 and its potential targeting drug, Tipifarnib, as promising molecular markers and therapeutic candidates for PTC. The hub gene CCND1 and its targeting drug candidate Tipifarnib may contribute to PTC treatment.

Communication between the vascular endothelium and peripheral leukocytes is an important process controlling inflammatory responses in the brain. Increased plasma levels of CTSD (cathepsin D) have been associated with vascular events, but whether circulating CTSD may affect the functional status of the endothelium remains unknown. To resolve this issue, two groups of transgenic hCTSDhi mice with high levels of circulating CTSD were subjected to traumatic and ischemic injury, respectively. Then, single-cell RNA sequencing was performed to characterize gene expression changes in the brains of hCTSDhi mice. Additionally, transgenic CTSDMono knockout mice with reduced plasma CTSD levels were generated to investigate whether CTSD downregulation confers protection against ischemic injury and traumatic brain injury-induced brain damage. We found the hCTSDhi mice showed increased brain neutrophil infiltration in response to the brain injury. Severe motor deficit and delayed behavioral recovery were observed in hCTSDhi mice after brain traumatic and ischemic injury. Mechanistically, the circulating CTSD was characterized as the nonenzymatic prototype CTSD, pro-CTSD. We further found the circulating nonenzymatic pro-CTSD was able to activate brain endothelium by upregulating VCAM-1 (vascular cell adhesion molecule 1) expression, which is necessary for the transmigration of neutrophils into the brain. Furthermore, genetic reduction of CTSD effectively attenuated the ischemic injury-induced neutrophil infiltration and motor deficits. Taken together, these results demonstrate that circulating prototype CTSD exacerbates the injury-induced brain damage by upregulating brain endothelial VCAM-1 and promoting neutrophil transmigration into the brain.

L1 cell adhesion molecule (L1CAM, CD171) is a transmembrane glycoprotein important for nervous system development. Conversely, L1CAM is overexpressed in many human solid tumors with poor prognosis. Nonclinical safety evaluation and pharmacokinetics (PK) of Ab612, a human anti-L1CAM monoclonal antibody (mAb), were conducted to support a first-in-human (FIH) clinical trial for the treatment of L1CAM overexpressing tumors. A tissue cross-reactivity (TCR) assessment showed that Ab612 exhibited staining in various tissues from mouse, rat, canine, cynomolgus monkey, and human, including those associated with peripheral nerves, myenteric plexus, spinal nerve roots, and certain cell types, such as mononuclear cells (lymphocytes), cardiac Purkinje fibers, and epithelial cell in the lung and kidney. These findings were consistent with the reported expression of the L1CAM by these cell types. Dose range-finding (DRF) studies were conducted in rats and cynomolgus monkeys at doses up to 500 and 400 mg/kg, respectively, by intravenous (IV) administration once weekly for 2 weeks. Results showed no treatment-related adverse findings, and the maximum tolerated dose (MTD) was the highest dose tested. Four-week repeat-dose toxicity studies were conducted in rats and cynomolgus monkeys at doses up to MTD, by IV administration once weekly for 4 weeks with a 28-day recovery period. Results showed no treatment-related adverse findings, and the no-observed-adverse-effect-level (NOAEL) was the highest dose tested. Single dose PK studies in rats and cynomolgus monkeys with doses of 5–100 and 5–50 mg/kg, respectively, confirmed the PK in the expected range for mAbs. These preclinical data indicate no safety concerns and provide adequate safety margins for the planned dose levels in the FIH trial.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00262-025-04142-9.

Clinical trials have shown favorable effects of exercise on frailty, supporting physical activity (PA) as a treatment and prevention strategy. Proteomics studies suggest that PA alters levels of many proteins, some of which may function as molecules in the biological processes underlying frailty. However, these studies have focused on structured exercise programs or cross-sectional PA-protein associations. Therefore, the effects of long-term PA on frailty-associated proteins remain unknown. Among 14,898 middle-aged adults, we emulated a target trial that assigned individuals to either (i) achieve and maintain the recommended PA level (≥ 150min/week of moderate-to-vigorous physical activity [MVPA]) through 6 (± 0.3) years of follow-up or (ii) follow a "natural course" strategy, where all individuals engage in various amounts of habitual MVPA. We estimated the effects of long-term adherence to recommended MVPA versus the natural course strategy on 45 previously identified frailty-associated proteins at the end of the follow-up using inverse probability of weighting (IPW) and iterative conditional expectations (ICE). We found that long-term adherence to recommended MVPA improved the population levels of many frailty-associated proteins (ranged from 0.04 to 0.11 standard deviation); the greatest benefits were seen in proteins involved in the nervous system (e.g., voltage-dependent calcium channel subunit alpha-2/delta-3 [CACNA2D3], contactin-1 [CNTN1], neural cell adhesion molecule 1 [NCAM1], and transmembrane protein 132D [TMEM132D]) and inflammation (e.g., high-temperature requirement serine protease A1 [HTRA1] and C-reactive protein [CRP]). Our findings suggest improved nervous system and reduced inflammation as the biological basis of long-term engagement in adequate PA as an intervention strategy for frailty.

Background Polydatin, a natural component of Polygonum cuspidatum, exhibits potent anti-metabolic properties. The treatment with Poly (10 µm/L) effectively reversed the high glucose (HG)-induced reduction in acetylcholine (ACh)-elicited vasodilation in the aortas of Sprague-Dawley rats. Methods Male Sprague-Dawley rats were used to evaluate the effects of polydatin on endothelial function under HG conditions. Endothelium-dependent relaxation (EDR) was assessed in isolated thoracic aortic rings using ACh, with or without L-NAME or tempol. Human umbilical vein endothelial cells (HUVECs) were also treated under normal glucose (NG), HG, or HG + polydatin conditions. Gene expression (NLRP3, VCAM-1, GAPDH) was measured by RT-PCR, while protein levels of eNOS, iNOS, NLRP3, VCAM-1, and GAPDH were analyzed by western blotting. Results HG significantly impaired ACh-induced EDR in rat aortic rings, while polydatin (10 µmol/L) restored vascular responsiveness. Mechanistically, polydatin upregulated eNOS and suppressed iNOS expression, and its vasoprotective effects were partially inhibited by L-NAME, indicating nitric oxide (NO) pathway involvement. In both aortic tissues and HUVECs, HG markedly increased NLRP3 and VCAM-1 expression, which was effectively reversed by polydatin, indicating its anti-inflammatory action. Conclusion Polydatin counteracts hyperglycemia-induced endothelial dysfunction by enhancing eNOS-dependent NO signaling to restore vasodilatory capacity, while inhibiting NLRP3 inflammasome activation and downstream VCAM-1 expression to attenuate vascular inflammation. These dual mechanisms position polydatin as a therapeutic agent for preserving vascular function in diabeticconditions.

AimsThe plasma protein soluble vascular cell adhesion molecule 1 (sVCAM-1) has been suggested as a biomarker for atrial fibrillation (AF). This study aimed to evaluate sVCAM-1 as a marker of AF and heart failure (HF) risk in the UK Biobank, incorporating genetic risk.Methods and resultsParticipants were included from 2006 to 2010. End of follow-up was 2023. Outcomes were incident AF and HF. Hazard ratios (HRs) per standard deviation increase in sVCAM-1 were assessed using Cox proportional hazard regression models. In sub-analyses, the cohort was stratified by tertiles of polygenic risk score (PRS) of AF and sVCAM-1. Associations between sVCAM-1 and cardiac magnetic resonance imaging measures were assessed in a sub-cohort. Among 48 495 included individuals, 54.6% were women. Median age at enrollment was 58 (50–63) years. During follow-up, 3484 were diagnosed with AF and 1937 with clinically diagnosed HF. Increasing sVCAM-1 levels were associated with rates of AF [HR: 1.72, 95% confidence interval (CI): 1.54–1.91] and HF (HR: 2.04, 95% CI: 1.78–2.34). In the highest sVCAM-1 tertile, 10-year cumulative incidence for AF and HF were 6.44% (95% CI: 6.05–6.82) and 3.01% (95% CI: 2.74–3.29), respectively. Stratified by tertiles of AF PRS and sVCAM-1 levels, a dose–response-like relationship emerged. In the imaging sub-cohort (n = 933), higher sVCAM-1 levels were associated with a reduced LAEF (β: −2.51, 95% CI: −4.33 to −0.70).ConclusionHigher sVCAM-1 levels were associated with AF and HF and lower LAEF. Integration of an AF PRS with sVCAM-1 levels identified a dose–response-like relationship with risk of AF.

The treatment of morphine addiction remains a significant clinical challenge, and the development of novel pharmacotherapies for opioid use disorder (OUD) is imperative. Agmatine, an endogenous neuromodulator, has promising antiaddictive potential, although its precise mechanisms remain incompletely characterized. In this study, a single morphine-induced behavioral sensitization model was established in mice, and immunofluorescence staining, transmission electron microscopy (TEM), RNA sequencing and network pharmacology were used to explore the mechanism of the anti-morphine addiction effects of agmatine. We found that agmatine improved morphine-induced behavioral sensitization without affecting spontaneous activity in mice and improved the changes in synapses in the NAc induced by morphine exposure. Network pharmacological analysis revealed that the key targets associated with agmatine-morphine dependence included TNF-α, IL-6 and IL-1β. Morphine exposure can lead to increased expression of these inflammatory factors, which are closely related with the M1 microglia. Agmatine administration significantly reduced morphine-induced neuroinflammation and activation of microglia. RNA sequencing revealed that the hub genes included TEK receptor tyrosine kinase (TEK), cadherin 5 (CDH5), platelet and endothelial cell adhesion molecule 1 (PECAM1) and so on, which are closely related to endothelial adhesion and angiogenesis. Morphine exposure can downregulate the expression of VE-cadherin, Pecam1, claudin-5, occludin and ZO-1, disrupt the integrity of the BBB and increase its permeability, whereas agmatine can protect the BBB. Agmatine reversed morphine induced BBB leakage and reduced NAc infiltration of peripheral cytokines. This study revealed that agmatine mitigates morphine-induced behavioral sensitization through anti-inflammatory and BBB protection in the NAc and thus provides mechanistic evidence for the development of therapeutic agents for OUD.

The discovery of novel marine natural products and their sustainable application continue to be vital focuses in marine biological research. The aim of this study is to investigate the inhibitory effect of the compound 5Z-7-Oxozeaenol isolated from the fungus Curvularia sp. MDCW-1060 on the proliferation of MDA-MB-231 cells and its molecular mechanism. A series of functional assays, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, Transwell migration, and colony formation, were employed to evaluate the effects of 5Z-7-Oxozeaenol on cellular viability, apoptosis, migration, and clonogenicity. The RNA sequencing (RNA-seq) coupled with bioinformatic analysis was conducted to identify affected differentiated gene expression and signaling pathways. The molecular docking was performed to predict potential protein targets, and Western blot was used to validate expression and phosphorylation levels of key signaling molecules. The results demonstrated that 5Z-7-Oxozeaenol significantly suppressed proliferation and migration while promoting apoptosis in MDA-MB-231 cells. The transcriptomic analysis indicated enrichment in pathways related to cancer, cytokine–cytokine receptor interaction, MAPK and PI3K-Akt signaling, and cell adhesion molecules. The molecular docking suggested a high binding affinity between 5Z-7-Oxozeaenol and PTPRN. While Western blot analysis confirmed the downregulation of phosphorylated FAK, PI3K, Akt, and MAPK, along with reduced cyclin D1 expression. Additionally, 5Z-7-Oxozeaenol upregulated the pro-apoptotic proteins p53 and cleaved caspase-3. In conclusion, 5Z-7-Oxozeaenol exerts potent antitumor effects on MDA-MB-231 cells through multi-pathway inhibition and induction of apoptosis, highlighting its potential as a marine-derived therapeutic candidate for breast cancer treatment.