Cell Biochemistry and Function最新文献

{"title":"Integrated RNA Sequencing and Multi-Bioinformatics Analyses Reveal the Molecular Mechanisms Underlying the Anti-Breast Cancer Effects of the Fritillariae Thunbergii Bulbus–Bolbostemmatis Rhizoma Herb Pair","authors":"Quan Tang,&nbsp;Dong Niu,&nbsp;He Li,&nbsp;Heng Zhou Zhu,&nbsp;Chun Hui Jin,&nbsp;Guo Qing Zhao,&nbsp;Xiao Dan Zhu","doi":"10.1002/cbf.70285","DOIUrl":"10.1002/cbf.70285","url":null,"abstract":"<p>Breast cancer (BC) is a highly heterogeneous malignancy with complex molecular mechanisms, highlighting the need for effective biomarkers and therapeutic targets. The Fritillariae Thunbergii Bulbus–Bolbostemmatis Rhizoma (ZBM–TBM) herb pair has been used in the treatment of BC, although its potential molecular mechanisms remain incompletely understood. In this study, an integrated strategy combining transcriptomic analysis, machine learning, liquid chromatography–tandem mass spectrometry (LC–MS/MS), network pharmacology, molecular docking, molecular dynamics (MD) simulations, and single-cell virtual knockout analysis was employed to identify BC-associated molecular biomarkers and explore the potential mechanisms underlying the effects of ZBM–TBM. Integration of weighted gene co-expression network analysis with least absolute shrinkage and selection operator regression, random forest, and support vector machine–recursive feature elimination identified EPCAM as the only common core gene. EPCAM was significantly upregulated in BC tissues and showed favorable diagnostic performance (AUC = 0.903), while high EPCAM expression was associated with shorter overall survival (log-rank P = 0.032). Functional analyses indicated that EPCAM was associated with tumor-related and immune-related biological processes, including cell cycle regulation, DNA replication, and immune regulation. LC–MS/MS analysis identified 32 major active constituents of ZBM–TBM, and subsequent network pharmacology analysis identified 33 overlapping targets and 10 hub genes enriched in multiple tumor- and immune-related signaling pathways, including the Notch, IL-17, HIF-1, and TGF-β signaling pathways. Although ZBM–TBM did not directly target EPCAM in the predicted target network, computational analyses indicated functional associations between EPCAM and hub gene-associated regulatory networks. Molecular docking and MD simulations further suggested that peiminine may represent a potential active constituent, exhibiting favorable predicted binding characteristics with multiple candidate targets, particularly AURKA. Single-cell virtual knockout analysis showed that computational perturbation of AURKA was associated with alterations in cell cycle-, extracellular matrix-, and cell adhesion-related processes, supporting its potential functional relevance at the cellular level.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Regulation of Bone Homeostasis in Osteoporosis: Mechanisms, Evidence Gaps, and Translational Prospects","authors":"Minjuan Du,&nbsp;Leisheng Wang","doi":"10.1002/cbf.70293","DOIUrl":"10.1002/cbf.70293","url":null,"abstract":"<p>Osteoporosis arises from an imbalance among osteoblast-mediated bone formation, osteoclast-mediated bone resorption, and osteocyte-directed mechanosensory control, but the molecular events that connect aging, hormonal change, inflammation, and mechanical unloading to bone loss remain incompletely resolved. Epigenetic mechanisms, including DNA methylation, histone modifications, non-coding RNAs (ncRNAs), and RNA modifications, provide one route through which environmental and cellular signals reshape bone-cell function. This review summarizes current evidence linking epigenetic regulation to osteoblasts, osteoclasts, and osteocytes; distinguishes human, animal, and in vitro evidence; and evaluates the translational maturity of proposed biomarkers and therapies. DNA methylation and histone modifications have strong mechanistic support in bone-cell differentiation models, whereas ncRNA and N6-methyladenosine (m6A) pathways are expanding rapidly but remain largely preclinical. Blood-based methylation or RNA signatures and epigenetic therapies are promising but should be considered exploratory until validated in prospective cohorts, fracture-related endpoints, and bone-cell-specific intervention studies.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUMOylation-Dependent Repression of BIRC7 by DNMT3a Suppresses Papillary Thyroid Carcinoma Progression","authors":"Kunpeng Liu,&nbsp;Zijie Su,&nbsp;Hongguang Li","doi":"10.1002/cbf.70290","DOIUrl":"10.1002/cbf.70290","url":null,"abstract":"<p>Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy, and while most patients respond well to standard therapies, a subset displays aggressive behavior, including lymph node metastasis and recurrence. The molecular mechanisms underlying PTC progression remain incompletely understood. Here, we identify baculoviral IAP repeat-containing 7 (BIRC7) as a pro-oncogenic factor upregulated in PTC tissues, particularly in metastatic tumors. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) dataset and validation in clinical samples revealed a strong inverse correlation between BIRC7 expression and DNA methylation levels at its promoter. Mechanistically, we demonstrate that the DNA methyltransferase DNMT3a directly binds to the BIRC7 promoter and represses its transcription via promoter methylation. Pharmacological inhibition or siRNA-mediated knockdown of DNMT3a leads to hypomethylation and transcriptional activation of BIRC7. Importantly, we show that DNMT3a undergoes SUMOylation, which negatively regulates its binding to the BIRC7 promoter. Inhibition of SUMOylation enhances DNMT3a chromatin occupancy and reduces BIRC7 expression. Functionally, BIRC7 promotes PTC cell proliferation and migration, while DNMT3a overexpression reverses these phenotypes in vitro and suppresses BIRC7-mediated tumor growth in vivo. Our study uncovers a previously unrecognized SUMOylation-dependent epigenetic regulatory axis wherein DNMT3a represses BIRC7 transcription. These findings establish BIRC7 as an epigenetically regulated oncogene in PTC and suggest that modulating DNMT3a SUMOylation may represent a novel therapeutic strategy for aggressive PTC.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prunetin Attenuates Dexamethasone-Induced Pancreatic β-Cell Apoptosis: Modulation of Oxidative Stress and MAPK Signaling but Not Phosphorylated C-Abl Levels","authors":"Thaksaon Kittipassorn,&nbsp;Nawarat Rattanajearakul,&nbsp;Petcharee Maneethorn,&nbsp;Namoiy Semprasert,&nbsp;Suwattanee Kooptiwut","doi":"10.1002/cbf.70292","DOIUrl":"10.1002/cbf.70292","url":null,"abstract":"<p>Dexamethasone has been reported to induce pancreatic β-cell apoptosis, which may contribute to steroid-induced diabetes following long-term glucocorticoid therapy. Although prunetin, a natural isoflavone, has been shown to attenuate dexamethasone-induced pancreatic β-cell apoptosis with suppression of p53 signaling as an associated pathway, the involvement of other signaling pathways remains unclear. This study aimed to investigate whether prunetin-mediated attenuation of dexamethasone-induced β-cell apoptosis was associated with changes in phosphorylated c-Abl (p-c-Abl) levels, oxidative stress, and MAPK signaling pathways. The rat insulinoma cell line INS-1 was treated with dexamethasone in the presence or absence of prunetin, followed by Annexin V-FITC/propidium iodide staining, western blotting, superoxide measurement, and caspase-3/7 activity assays. Dexamethasone induced early apoptosis, reduced p-c-Abl and glutathione S-transferase P1 (GSTP1) levels, increased superoxide generation, elevated phosphorylated JNK and p38 levels, decreased phosphorylated ERK1/2 levels, and stimulated caspase-3/7 activity, whereas total c-Abl levels remained unchanged. Prunetin pre-treatment before dexamethasone administration significantly reduced early apoptosis, restored GSTP1 expression, attenuated oxidative stress, and modulated MAPK signaling by decreasing phosphorylated JNK and p38 levels while increasing phosphorylated ERK1/2 levels. However, prunetin did not restore the dexamethasone-induced reduction in p-c-Abl levels. These findings suggest that prunetin attenuates β-cell apoptosis induced by dexamethasone and that this effect is associated with modulation of oxidative stress, GSTP1 expression, and MAPK signaling pathways, but not with restoration of reduced p-c-Abl levels. Collectively, this study extends current knowledge of signaling changes associated with prunetin in glucocorticoid-induced β-cell injury.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment","authors":"Yixuan Chen,&nbsp;Wenming Huang,&nbsp;Mingxuan Tang,&nbsp;Xiaotao Wang","doi":"10.1002/cbf.70286","DOIUrl":"https://doi.org/10.1002/cbf.70286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Multiple myeloma (MM) is a malignant plasma cell disorder, and despite substantial improvements in prognosis achieved through chemotherapy, immunotherapy, and autologous stem cell transplantation, most patients ultimately develop relapsed or refractory disease. Drug resistance (DR) is increasingly recognized as a dynamically evolving ecosystem shaped by tumor-intrinsic plasticity and continuous remodeling of the bone marrow microenvironment (BMME), rather than as a single molecular lesion. This review summarizes the major mechanisms of resistance across key drug classes, including alterations in drug targets and signaling nodes, rewiring of apoptotic, proteostatic, and metabolic circuits, and BMME-dependent protection. We highlight how these processes converge on a limited set of survival hubs and collectively raise the apoptotic threshold under therapeutic pressure. The key to overcoming DR is to conceptualize it as an evolving ecosystem, thereby enabling rational, mechanism-based combination and sequencing strategies that may prolong progression-free survival and move MM closer to a functional cure.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Role of FGF9/ERK/MMP9 Pathway in Age-Related Cataract and in (-)-Epigallocatechin-3-gallate Protecting Lens Epithelial Cells From Apoptosis","authors":"Jiale Yu,&nbsp;Yifan Wu,&nbsp;Jianan Wu,&nbsp;Cuige Shi,&nbsp;Xiaofeng Chen,&nbsp;Ying Wei,&nbsp;Lina Guan,&nbsp;Jialing He,&nbsp;Yue Zhang,&nbsp;Zihan Xiang,&nbsp;Dongmei Su,&nbsp;Shanshan Hu,&nbsp;Xu Ma","doi":"10.1002/cbf.70289","DOIUrl":"https://doi.org/10.1002/cbf.70289","url":null,"abstract":"<p>Age-related cataract (ARC) is the most prevalent form of cataract. Oxidative stress-induced apoptosis of lens epithelial cells (LECs) is a major pathogenic factor, but its underlying molecular mechanisms remain incompletely understood. This study investigated the roles of FGF9, <i>ERK</i>, and MMP9 in ARC and examined whether the FGF9<i>/ERK/</i>MMP9 pathway is involved in the protective effects of (-)-epigallocatechin-3-gallate (EGCG) against LEC apoptosis. FGF9 and MMP9 were downregulated at both the mRNA and protein levels in ARC mice and H₂O₂ (200 µM)-treated HLE-B3 cells as determined by immunohistochemistry, Western blotting and qRT-PCR. FGF9 overexpression increased cell viability and reduced apoptosis in H₂O₂-treated HLE-B3 cells, as demonstrated by CCK-8 and Hoechst 33342 staining. EGCG treatment improved cell viability and increased FGF9 expression in H₂O₂-treated cells and lens tissues from ARC mice. Conversely, FGF9 knockdown attenuated the protective effect of EGCG. Further experiments suggested that FGF9 may contribute to the anti-apoptotic effects of EGCG by modulating ERK phosphorylation and MMP9 expression. ERK activation by TBHQ increased the viability of H₂O₂-treated HLE-B3 cells, whereas ERK inhibition with PD98059 attenuated the protective effects of EGCG and decreased MMP9 expression. Moreover, MMP9 knockdown increased cleaved caspase-9 expression and was accompanied by increased apoptosis in LECs. These findings suggest that the FGF9<i>/ERK/</i>MMP9 pathway is involved in oxidative stress-induced LEC apoptosis and may contribute, at least in part, to the protective effects of EGCG in experimental models of ARC.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of CREB1 by Mycobacterium Tuberculosis Transcriptionally Activates TREM2 to Promote Macrophage M2 Polarization","authors":"Yufeng Zhu,&nbsp;Mingzhong Xu,&nbsp;Danxia Liu,&nbsp;Wei Ning,&nbsp;Miaomiao Wang,&nbsp;Feifan Huang,&nbsp;Zhen An,&nbsp;Jingsong Qiu,&nbsp;Xian Tang,&nbsp;Peipei Wang,&nbsp;Bin Tian,&nbsp;Lan Wen","doi":"10.1002/cbf.70284","DOIUrl":"10.1002/cbf.70284","url":null,"abstract":"<p>Tuberculosis, caused by Mycobacterium tuberculosis (MTB), affects approximately 25% of people globally as latent infection (LTBI). Although macrophage CREB activation promotes MTB survival, the underlying mechanisms remain unclear. This study reveals, for the first time, how MTB modulates M2 macrophage polarization through the CREB1/TREM2 signaling pathway. Mononuclear macrophages were isolated from clinical sample. Flow cytometry was used to determine the M2 polarization ratio. The expression of TNF-α, IL-10, and IL-1β was determined by ELISA. The mRNA expression of iNOS, IL-1β, CD206, Arg-1, IL-10, CREB1, and TREM2 was assessed by qPCR. The protein expression of CREB1, CD206, Arg-1, IL-10, and TREM2 was evaluated by western blot. The colony-forming unit (CFU) assay was used to detect the survival of MTB. CHIP and Dual-luciferase reporter assays were used to confirm the binding of CREB1 and TREM2. Clinical sample analysis revealed that the expression levels of CREB1 and TREM2 in peripheral blood mononuclear macrophages (PBMCs) were significantly upregulated in tuberculosis patients. Following H37Rv infection, an increase in the M2 macrophage proportion was observed. Infection with MTB also elevated the protein level of IL-10, as well as CREB1 mRNA and protein expression. Transfecting sh-CREB1 into macrophages or adding CREB inhibitors 666-15 markedly reduced intracellular MTB CFU counts, implying a potential restrictive effect on viable MTB load within macrophages. Knockdown of TREM2 similarly decreased MTB CFU burden and restrained macrophage M2 polarization. Furthermore, transfecting sh-CREB1 into macrophages can suppress the proliferation of MTB within macrophages, and these effects could be further counteracted by the action of oe-TREM2. These results elucidated that MTB promoted M2 macrophage polarization through CREB1/TREM2.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TET2 as a Context-Dependent Epigenetic Integrator in Clonal Hematopoiesis, Inflammation, Cancer, and Immunotherapy","authors":"XiaoJie Liu,&nbsp;Jiangchen Liu,&nbsp;Liu Feng,&nbsp;Dan Xu,&nbsp;Xianling Wei,&nbsp;Dekuai Tong","doi":"10.1002/cbf.70287","DOIUrl":"https://doi.org/10.1002/cbf.70287","url":null,"abstract":"<p>Ten-Eleven Translocation 2 (TET2) is an Fe(II)- and α-ketoglutarate-dependent dioxygenase that initiates active DNA demethylation by oxidizing 5-methylcytosine (5mC). Beyond this enzymatic role, TET2 links DNA methylation dynamics with chromatin regulation, cellular metabolism, immune-cell identity, and treatment response in a context-dependent manner. Loss-of-function mutations in TET2 are among the most frequent genetic events in age-related clonal hematopoiesis of indeterminate potential (CHIP), where they are associated with higher risks of hematological malignancies and cardiovascular disease. Human genetic and clinical studies support these associations, while experimental models suggest that mutant hematopoietic clones can promote myeloid inflammatory programs through enhancer remodeling, NLRP3 inflammasome activation, IL-1β/IL-6 signaling, and altered inflammatory resolution. In solid tumors and cancer therapy, TET2 has more variable effects: tumor-cell-intrinsic TET2 loss can contribute to immune escape or therapeutic resistance in selected settings, whereas TET2 disruption in engineered T cells can enhance memory-like persistence and anti-tumor activity, with possible long-term oncogenic risk. This narrative, mechanism-oriented review integrates current evidence on TET2 biology across clonal hematopoiesis, inflammation, cancer, and immunotherapy. We focus on evidence level, cell type, direction of TET2 alteration, and metabolic or therapeutic context as determinants of divergent TET2 functions. TET2 has traditionally been described as a DNA demethylation enzyme, but recent studies increasingly place it among context-dependent regulators of immune and disease phenotypes. The unresolved issue is why TET2 loss, inhibition, activation, or engineered deletion can produce distinct, and sometimes opposing, effects in hematopoietic stem/progenitor cells, macrophages, tumor cells, neurons, microglia, and CAR-T cells. This review uses four variables—cell type, direction of alteration, functional layer, and microenvironmental or therapeutic context—to interpret evidence from CHIP, hematologic malignancies, cardiovascular inflammation, solid tumors, and immunotherapy.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Terpenoids in Advancing Biofilm-Mediated Cancer Prevention: Antibiofilm Cascade, Molecular Crosstalk, and Nano-Facilitated Functional Delivery","authors":"Saikat Mazumder,&nbsp;Aditi Dey,&nbsp;Debasmita Bhattacharya,&nbsp;Dibyajit Lahiri,&nbsp;Moupriya Nag,&nbsp;Sudhriti Maity,&nbsp;Navin Kumar,&nbsp;Soumya Pandit,&nbsp;Vaseem Raja,&nbsp;Shubham Sharma,&nbsp;Shashi Prakash Dwivedi,&nbsp;Mithul Rajeev,&nbsp;Juwita Ratna Dewi,&nbsp;Lola Sanayeva,&nbsp;Dilbar Azimova","doi":"10.1002/cbf.70281","DOIUrl":"10.1002/cbf.70281","url":null,"abstract":"<p>The role of microbes in cancer is gaining attention these days, especially in the context of tumor-associated biofilms and dysbiotic microbiota. Biofilm-producing microorganisms, such as <i>Fusobacterium nucleatum</i> and <i>Helicobacter pylori</i>, trigger oncogenic inflammation and immune evasion in tumor initiation and progression, and in the development of chemoresistance, through the activation of the NF-κB, STAT3, and β-catenin pathways. Dietary terpenoids are a structurally diverse group of antitumor and antibiofilm plant metabolites. Monoterpenoids, sesquiterpenoids, and triterpenoids are known to inhibit quorum sensing, the biosynthesis of extracellular polymeric substances (EPS), and the expression of biofilm-associated virulence factors, proposing an unexplored convergence among antibiofilm and anticancer mechanisms. Importantly, the biofilm structure (thickness, developmental stage, EPS density) affects the efficacy of terpenoids, affecting diffusion, microbial persistence, and therapeutic susceptibility. The quorum-sensing disruption is more effective in the early stages of biofilms, while high concentrations of EPS in mature, thick biofilms will require more penetration to disrupt quorum sensing. Innovative functional food matrices, including nano-enabled delivery systems, are emerging strategies to improve bioavailability and microbiome modulation of terpenoids. Furthermore, nano-formulations allow better penetration in dense biofilm matrices, protect terpenoids from early degradation, and allow prolonged and focused drug release in the tumor microenvironment associated with biofilms. Combining precision nutrition with microbiome-informed dietary strategies can be used to prevent and treat cancer. The present review combines studies linking biofilm-driven carcinogenesis with terpenoid-mediated antibiofilm–anticancer pathways and nano-mediated functional delivery and biofilm penetration, including highlighting the potential for microbiome modulation in cancer therapy.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Efficacy of Metronomic Doxorubicin and Low Dose of Gamma Radiation on Breast Cancer Model","authors":"Ibrahim Y. Abdelrahman,&nbsp;Mostafa Saif-Elnasr,&nbsp;Zeinab R. Attia,&nbsp;Rania A. Abd El Azeem,&nbsp;Eman Khalifa,&nbsp;Mostafa A. Askar","doi":"10.1002/cbf.70278","DOIUrl":"10.1002/cbf.70278","url":null,"abstract":"<p>Breast cancer is the most common malignancy in females internationally. Doxorubicin (DOX) has been well-thought-out as the most effective regimen for breast cancer treatment for several years. The chronic side effects of DOX obligate us to control the dosage that can be used, although its efficacy. Radiotherapy is a vigorous regimen in breast cancer treatment, but correlated side effects are determining factors for a successful recovery. Combined metronomic chemotherapy and radiotherapy, at low doses, can reduce the side effects of single-modality treatments. We have studied the dose 1.8 mg/kg twice per week for 8 weeks of DOX singly or with 0.5 Gy fractionated doses of gamma radiation on inducing cell death, cell cycle arrest, and apoptosis, and also P53, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), and caspase-3 gene expression in an animal breast cancer model. Treatment with DOX resulted in upregulation of apoptosis and downregulation of cell division at an accumulated dose of 0.5 Gy, as well as downregulation of Bcl-2 gene expression and upregulation of p53, Bax, and caspase-3 gene expression in animals bearing breast cancer. In addition, DOX in combination with radiation decreased the tumor size. A metronomic dose of DOX, when used with a low dose of gamma radiation, with the least side effects, could be a successful treatment for breast cancer in clinical trials.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"44 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}