Journal of Cancer最新文献

{"title":"Erratum: Overexpression of Platelet-Derived Growth Factor Receptor Α <i>D842V</i> Mutants Prevents Liver Regeneration and Chemically Induced Hepatocarcinogenesis via Inhibition of MET and EGFR: Erratum.","authors":"Zhao-Qing Du, Jian Dong, Mu-Xing Li, Jian-Fei Zhang, Jian-Bin Bi, Yi-Fan Ren, Li-Na Zhang, Rong-Qian Wu, Satdarshan P S Monga, Yi Lv, Xu-Feng Zhang, Hai-Chen Wang","doi":"10.7150/jca.140353","DOIUrl":"https://doi.org/10.7150/jca.140353","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/jca.44492.].</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1546"},"PeriodicalIF":3.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation Patterns Define Clinical Heterogeneity in Acute Myeloid Leukemia.","authors":"Zhengrong Xu, Ying Zheng, Yi Zheng, Yanyan Yao, Haili Geng, Xiaofan Li, Shao-Yuan Wang, Lili Pan","doi":"10.7150/jca.135267","DOIUrl":"10.7150/jca.135267","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a molecularly heterogeneous malignancy where next-generation sequencing (NGS) has revolutionized risk stratification and treatment paradigms. However, the interplay between mutation cooperativity, clinical phenotypes, and biochemical markers of organ dysfunction remains poorly characterized. This study investigates how co-mutational patterns influence hematological/biochemical parameters and survival outcomes in AML.</p><p><strong>Methods: </strong>In this single-center retrospective study (2017-2024), 1,416 non-M3 AML patients with NGS-confirmed somatic mutations were analyzed. Clinical parameters included hematologic parameters, biochemical markers, and survival outcomes. Multivariate Cox models, Kaplan-Meier analysis, propensity score matching (1:4), and Cohen's d effect sizes were employed to assess mutation-clinical correlations.</p><p><strong>Results: </strong>A higher mutational burden was associated with older age, elevated platelets, and renal impairment, with <i>DNMT3A</i> mutation identified as an independent factor for renal impairment. Multivariable analysis identified higher mutational burden, age, renal impairment, and high white blood cell counts as independent predictors of inferior survival. We identified novel co-occurring (e.g., <i>KRAS</i> and <i>PTPN11</i>; OR = 3.19; 95% CI, 2.97-3.42) or mutually exclusive (e.g., <i>CEBPA</i>-<i>bZIP</i> and <i>NPM1</i>; OR = 0.03; 95% CI, 0.01-0.17) gene pairs (all adjusted <i>P</i> <0.001). The <i>NPM1</i>/<i>IDH1</i> co-mutation elevated blast percentages in bone marrow and peripheral blood compared to either single mutation alone. Three novel triple-mutations were significantly associated with higher mortality: <i>IDH2</i>: <i>FLT3</i>-<i>ITD</i>: <i>NPM1</i> (HR = 4.68), <i>IDH2</i>: <i>SRSF2</i>: <i>ASXL1</i> (HR = 3.31), and <i>RUNX1</i>: <i>TET2</i>: <i>NRAS</i> (HR = 3.08) (all adjusted <i>P</i> <0.05).</p><p><strong>Conclusions: </strong>These findings support integrating genomic and biochemical profiling for AML management, as co-mutation patterns, particularly those affecting renal function, refine risk stratification and highlight the need for tailored monitoring and organ support.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1531-1545"},"PeriodicalIF":3.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucosamine Use and Its Association with Colorectal Cancer and Mortality: A Systematic Review and Meta-Analysis.","authors":"Yiling Yan, Manrong Xu, Ruixin Wang, Shengdi Lu, Yun Shen, Feng Liu","doi":"10.7150/jca.133131","DOIUrl":"10.7150/jca.133131","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and aim: &lt;/strong&gt;This systematic review and meta-analysis aimed to evaluate whether habitual glucosamine use is associated with colorectal cancer risk and survival outcomes in the general population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Following PRISMA 2020 guidance, we systematically searched PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception to January 10, 2026. Prospective cohort studies comparing glucosamine users with non-users and reporting adjusted effect estimates were eligible. Two reviewers independently extracted data and assessed study quality using the Newcastle-Ottawa Scale. Adjusted hazard ratios or relative risks were pooled using fixed- or random-effects models based on heterogeneity quantified with I².&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From 347 records, 18 prospective cohort studies met eligibility criteria; five outcomes (colorectal cancer incidence, colorectal cancer-specific mortality, all-cause mortality, cardiovascular mortality, and overall cancer mortality) were quantitatively synthesized. Glucosamine use was associated with a lower incidence of colorectal cancer across 5 studies (pooled HR 0.87, 95% CI 0.82 to 0.92; I² = 36%). For colorectal cancer-specific mortality, the evidence was limited to only 2 studies with substantial heterogeneity (I² = 81%) and effect estimates in opposite directions, and the pooled estimate showed no clear association (pooled RR 0.99, 95% CI 0.57 to 1.71); this outcome should therefore be regarded as inconclusive. Glucosamine use was also associated with lower all-cause mortality in 4 studies (pooled HR 0.84, 95% CI 0.76 to 0.94; I² = 65%), lower cardiovascular mortality in 4 studies (pooled HR 0.82, 95% CI 0.75 to 0.89; I² = 44%), and a modest reduction in overall cancer mortality in 4 studies (pooled HR 0.94, 95% CI 0.91 to 0.98; I² = 7%). Results were stable in leave-one-out sensitivity analyses. All estimates represent associations derived from observational cohort studies and cannot establish causation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Current cohort evidence indicates that glucosamine use is associated with a modestly lower risk of developing colorectal cancer and with lower mortality from all causes, cardiovascular disease, and cancer overall. The evidence for colorectal cancer-specific mortality was based on only 2 studies with substantial heterogeneity and remains inconclusive. Because all included studies were observational, these findings represent associations rather than evidence of a causal protective effect. Given the modest effect sizes, healthy-user bias and residual confounding are plausible and possibly major explanations for the observed associations, and even a small degree of unmeasured confounding could account for part or all of them. Well-designed studies with improved exposure characterization, and ideally causal designs such as Mendelian randomization, are needed to determine whether these associations ","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1520-1530"},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Parameters influence Chemosensitivity in Gastric Cancer Cells.","authors":"Kai-Chun Hong, Yi-Chun Chen, You-Syuan Lou, Chia-Chi Tsai, Xu-Chen Liu, Lei-Ni Liang, Chih-Cheng Cheng, Hsin-Hsien Yu, Bor-Chyuan Su","doi":"10.7150/jca.137748","DOIUrl":"10.7150/jca.137748","url":null,"abstract":"<p><p>Mitochondria play crucial roles in the survival of malignant cells in gastric and other types of cancers, and many cancer treatments act at least in part via mitochondrial effects. Although several measurable mitochondrial parameters have been associated with sensitivity of certain cancer cells to treatments, it remains unclear how these parameters differ among cancer cells according to differentiation level and histological type. It also remains unclear whether and how the effects of chemotherapy on mitochondrial parameters might be associated with sensitivity to treatment. In this study, we compared mitochondrial parameters in a panel of gastric cancer cell lines with different characteristics, including AGS (moderately differentiated), SNU-1 (poorly differentiated), KATO III (signet ring cell carcinoma; SRCC), and NUGC-4 (SRCC). We examined differences in basal mitochondrial parameters between the cell lines and the impacts of chemotherapy on each parameter. Our results showed that each cell line showed a different response pattern to cisplatin and 5-fluorouracil. For example, cisplatin was much more effective than 5-fluorouracil at killing SNU-1 gastric cancer cells, while KATO III cells exhibited minimal responses to both chemotherapies. These patterns of cytotoxicity were closely aligned with mitochondrial membrane potential. The different gastric cancer cell lines also displayed differences in basal mitochondrial parameters, but the basal measurements did not directly correlate with sensitivity to chemotherapy. Nevertheless, sensitivity was associated with an integrated profile of basal levels and effects of chemotherapy on mitochondrial parameters. Thus, our study highlights the association between mitochondrial parameters and chemosensitivity among gastric cancer cells with diverse characteristics. These findings may guide the development of more precise treatment strategies and targeted therapies for distinct types of gastric cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1480-1490"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction as a Targetable Vulnerability in Gastric Cancer: From Carcinogenesis to Apoptosis (A Narrative Review).","authors":"Hsi-Lung Hsieh, Ming-Chin Yu, Hui-Ching Tseng, Yi-Hsuan Wu, Tzu-Hao Huang, Ming-Ming Tsai","doi":"10.7150/jca.131081","DOIUrl":"10.7150/jca.131081","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a major global health burden and is associated with high mortality worldwide. Current treatment integrates surgery, perioperative or systemic chemotherapy, molecularly targeted therapy, and immune checkpoint blockade; however, efficacy is frequently limited by intratumoral heterogeneity, metabolic plasticity, and therapeutic resistance. Mitochondria, as central regulators of cellular bioenergetics, redox homeostasis, and apoptotic signaling, are profoundly altered in GC. Tumor cells frequently exhibit enhanced aerobic glycolysis accompanied by suppressed oxidative phosphorylation, reflecting mitochondrial metabolic remodeling. Accumulating evidence indicates that mitochondrial dysfunction actively contributes to tumor initiation, progression, and therapeutic resistance in GC. Importantly, these mitochondrial alterations also create metabolic vulnerabilities that may be therapeutically exploitable. Both conventional chemotherapeutic agents and herbal-derived natural compounds have been reported to induce mitochondrial stress responses, including excessive reactive oxygen species (ROS) accumulation, mitochondrial membrane potential loss, and activation of mitochondria-dependent intrinsic apoptotic pathways. In this narrative review, we summarize the major molecular mechanisms underlying mitochondrial dysfunction in GC, highlight mitochondrial-associated prognostic biomarkers, and discuss emerging therapeutic strategies targeting mitochondrial pathways. Collectively, these insights emphasize mitochondrial dysfunction as a candidate therapeutic vulnerability and support further investigation of mitochondria-centered therapeutic strategies for GC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1445-1462"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKM2 is the Metabolic Checkpoint for Stemness Features in Head and Neck Cancer.","authors":"Wan-Hsuan Sun, Ta-Jung Peng, Hsueh-Jou Fang, Chia-Ling Chang, Yu-Wen Tang, Kuang-Hui Sun","doi":"10.7150/jca.132595","DOIUrl":"10.7150/jca.132595","url":null,"abstract":"<p><p>Owing to their self-renewal, differentiation capabilities, and increased chemoresistance, cancer stem cells (CSCs) are associated with poor prognosis and an elevated chance of relapse and metastasis. CSCs survive under therapy-imposed pressure and aggravate tumor malignancy through metabolic reprogramming, leading to treatment failure. The RNA level of pyruvate kinase isoenzyme M2 (<i>PKM2</i>) is increased in head and neck cancer (HNC) tissues and is linked to poor prognosis, whereas <i>PKM2</i> deletion was found to accelerate tumorigenesis and tumor growth <i>in vivo</i>, leading to a paradox between <i>PKM2</i> expression and tumorigenesis. To date, the role of PKM2 inhibition in HNC progression remains unclear. In the present study, we found that low PKM2 protein expression was significantly associated with later stages and higher grades of cancer in HNC tissues. Following <i>PKM2</i> silencing, HNC cells exhibited significantly increased ATP levels, decreased lactate production, and upregulated mitochondrial respiratory activity. In addition, <i>PKM2</i> knockdown promoted clonogenicity, motility, nuclear-activated β-catenin, CSC formation, and <i>in vivo</i> tumorigenicity in HNC cells. PKM2 inhibition further augmented stemness and resistance to chemotherapeutic drugs in HNC CSCs. Whole-genome transcriptome analysis of <i>PKM2</i>-knockdown CSCs revealed upregulation of differentially expressed genes (DEGs) in the Wnt signaling pathway. The present study concluded that decreased PKM2 is associated with aggressive clinicopathological features. PKM2 inhibition-promoted stemness may be mediated by increased nuclear β-catenin localization, which potentially contributes to tumorigenesis and disease progression in HNC. Our findings suggest that PKM2 modulates HNC stemness by linking metabolic rewiring with oncogenic signaling, highlighting its potential as a molecular target for adjuvant therapy in patients with HNC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1504-1519"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental co-exposure to microplastics and phenol may influence redox signaling and tumor microenvironment dynamics.","authors":"Chung-Yu Lin, Che-Hsin Lee","doi":"10.7150/jca.135514","DOIUrl":"10.7150/jca.135514","url":null,"abstract":"<p><p>Environmental exposure patterns have shifted from single-compound exposure to complex co-exposure scenarios. Among widespread pollutants, microplastics (MPs) and phenol may interact biologically despite their distinct physicochemical properties. Phenol is associated with oxidative stress-related toxicity, whereas MPs may serve as potential carriers and redox-active modifiers. This review proposes that MP-induced oxidative stress and phenol-mediated antioxidant disruption may jointly reshape redox-sensitive intracellular signaling under MPs-phenol co-exposure conditions, with mitogen-activated protein kinase (MAPK) pathways proposed as potential convergence nodes. Within this framework, MAPK signaling may link oxidative stress to hypoxia-inducible factor 1α (HIF-1α) stabilization, angiogenic responses, and tumor-associated processes, and may also facilitate NF-κB/STAT3-mediated inflammatory signaling and PD-L1 regulation. Because direct experimental evidence for these integrated mechanisms remains limited, this framework should be regarded as a biologically plausible and testable model rather than a confirmed causal pathway. This review highlights key knowledge gaps and future priorities for evaluating how complex environmental co-exposures may influence cancer progression and immune regulation.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1470-1479"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential influence of long non-coding RNA <i>NEAT1</i> genetic variants and expression levels on the progression of prostate cancer.","authors":"Cheng-En Mei, Chia-Yen Lin, Shian-Shiang Wang, Shih-Chi Su, Heng-Hsiung Wu, Lun-Ching Chang, Chih-Hsin Tang, Shun-Fa Yang","doi":"10.7150/jca.137994","DOIUrl":"10.7150/jca.137994","url":null,"abstract":"<p><p>Prostate cancer is a leading malignancy in men worldwide, with disease aggressiveness varying widely among patients. Long non-coding RNA NEAT1 has emerged as a key regulator of tumor progression, yet the impact of its genetic variants on prostate cancer susceptibility and aggressiveness remains unclear. In this study, we investigated the association of <i>NEAT1</i> polymorphisms with clinicopathological features in 693 prostate cancer patients. Patients were stratified by PSA levels (≤ 10 ng/mL vs. > 10 ng/mL), and genotypes of <i>NEAT1</i> rs3741384, rs512715, and rs3825071 were determined. Among the analyzed <i>NEAT1</i> SNPs, rs3825071 was significantly associated with PSA levels and perineural invasion in patients with prostate cancer. In the high-PSA subgroup, carriers of the CT and TT genotypes exhibited a lower likelihood of elevated PSA (> 10 ng/mL) (AOR = 0.794, p = 0.011) and a reduced risk of perineural invasion (OR = 0.470, p = 0.007). Functional analyses using the GTEx and TCGA datasets revealed genotype-dependent alterations in NEAT1 expression, with significant upregulation observed in prostate cancer tissues, particularly in cases with higher Gleason scores and lymph node metastasis. Collectively, our results suggest that <i>NEAT1</i> rs3825071 T alleles confer a protective effect and highlight its potential as a genetic biomarker for prostate cancer progression.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1463-1469"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Field cancerization in urothelial carcinoma: molecular alterations and clinical implications.","authors":"Xinni Ye, Junhao Chen, Hongqiong Li, Haonan Dong, Tianjiao Luo, Peng Chen, Haifeng Wang, Shi Fu","doi":"10.7150/jca.125266","DOIUrl":"10.7150/jca.125266","url":null,"abstract":"<p><p>Urothelial carcinoma (UC) is a common malignancy of the urinary tract and is characterized by frequent recurrence, particularly in patients with non-muscle-invasive disease. Recurrence has traditionally been explained by residual tumor cells, intraluminal seeding, or the outgrowth of disseminated clones. However, molecular studies have shown that urothelium that appears normal under routine histological examination may already harbor cancer-related alterations. These findings support the concept of field cancerization, whereby prolonged exposure to carcinogens, chronic inflammation, and other injurious stimuli produces a biologically altered urothelial field before overt malignancy becomes visible. In this review, we searched PubMed and Web of Science for relevant studies published up to January 2026. We focused on investigations of peritumoral tissue or histologically normal-appearing urothelium that reported molecular abnormalities associated with UC development or recurrence. Available evidence from sequencing, methylation profiling, spatial mapping, and multi-omics studies indicates that field changes may involve somatic mutations, copy-number alterations, epigenetic dysregulation, metabolic reprogramming, and remodeling of the local immune and stromal microenvironment. These changes may create a permissive background for clonal expansion, multifocal tumor development, and recurrence after treatment. Although the clinical definition and spatial extent of the urothelial field remain unsettled, molecular characterization of apparently uninvolved urothelium may help refine risk assessment beyond conventional histopathology. In particular, perioperative urinary tumor DNA testing may assist in identifying molecular residual disease and support more individualized surveillance or adjuvant treatment decisions.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1491-1503"},"PeriodicalIF":3.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective sensitivity of betel nut-related oral squamous cell carcinoma to evodiamine through cell cycle arrest, growth inhibition and apoptosis induction.","authors":"Yin-Che Lu, Kai-Liang Tang, Chih-Hsien Liao, Yi-Zhen Li, Chin-Ho Kuo, Pin-Tzu Chen, Shu-Hsin Chen, Ying-Ray Lee","doi":"10.7150/jca.136981","DOIUrl":"10.7150/jca.136981","url":null,"abstract":"<p><p>Head and neck cancer, particularly oral squamous cell carcinoma (OSCC), remains a major global health burden, with especially high incidence and mortality in Taiwan due to the widespread habit of betel quid chewing. Betel nut mediated OSCC (BN-OSCC) is characterized by aggressive clinical behavior, including increased risks of recurrence, metastasis, and poor survival outcomes, and exhibits limited responsiveness to conventional chemoradiotherapy. Therefore, the development of novel therapeutic agents and radiosensitizers is urgently needed. Evodiamine (EVO), a bioactive quinolone alkaloid isolated from <i>Evodia rutaecarpa</i>, has demonstrated broad anti-tumor activities across multiple cancer types, including inhibition of proliferation, suppression of metastasis, and induction of apoptosis. Although previous studies have reported the anti-OSCC effects of EVO through modulation of pathways such as Akt, EPRS1, and RAGE, its specific impact on BN-OSCC remains unclear. In this study, we investigated the anti-cancer effects of EVO in BN-OSCC and non-BN-OSCC cell lines. Our results demonstrate that EVO significantly inhibits cell viability and proliferation in a dose-dependent manner in BN-OSCC rather than non-BN-OSCC cells. Importantly, EVO induces apoptosis through activation of the caspase-dependent pathway, as evidenced by increased cleavage of caspase-3, caspase-9, and PARP. Furthermore, EVO treatment leads to mitochondrial dysfunction and enhances pro-apoptotic signaling, suggesting involvement of the intrinsic apoptotic pathway. Collectively, these findings indicate that EVO exerts potent anti-tumor effects in BN-OSCC cells by triggering caspase-dependent apoptosis. This study provides novel insights into the therapeutic potential of EVO and supports its development as a promising candidate for the treatment of betel nut mediated oral cancer.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1435-1444"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}