Recent patents on anti-cancer drug discovery最新文献

{"title":"LMNB1 and LMNB2 as Prognostic Risk Factors in Hepatocellular Carcinoma: Therapeutic Potential of GSK461364 via Downregulation of LMNB1 and LMNB2 Expression.","authors":"Hui Yong, Yingqi Zhou, Binhui Li, Wanren Yang, Mingxin Pan, Wenhao Suo, Jia Yao, Botian Ouyang, Zhiang Hu, Rongxia Li, Qing Peng, Xin Kang","doi":"10.2174/0115748928375684250716120144","DOIUrl":"https://doi.org/10.2174/0115748928375684250716120144","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to explore the potential of LMNB1 and LMNB2 as prognostic risk factors in hepatocellular carcinoma (HCC) and investigate small-molecule drugs targeting both for therapeutic application.</p><p><strong>Methods: </strong>LMNB1 and LMNB2 expression in HCC was assessed using TCGA data and validated in clinical specimens. Kaplan-Meier and Cox models evaluated prognostic relevance. Drug sensitivity screening using CTRP and GDSC databases highlighted GSK461364 (a selective PLK1 inhibitor), whose effects were validated in Hep3B and SK-HEP-1.</p><p><strong>Results: </strong>LMNB1 and LMNB2 were aberrantly up-regulated in HCC tissues and contributed to the poor prognosis of HCC patients. Co-expression modules and enriched pathways of LMNB1 and LMNB2 were linked to nuclear architecture and cell senescence, indicating their roles in genomic stability and cell cycle progression. GSK461364 was validated to inhibit the cell viability of HCC cells. It suppressed the expression of LMNB1 and LMNB2 but not PLK1, suggesting its anti-HCC effect depends on inhibition of LMNB1/2 rather than PLK1.</p><p><strong>Discussion: </strong>Our findings suggest that LMNB1 and LMNB2 could serve as prognostic biomarkers. GSK461364 likely exerts anti-HCC effects through suppression of LMNB1 and LMNB2 expression. Further in vivo validation and molecular mechanism studies are needed to establish its clinical utility.</p><p><strong>Conclusion: </strong>LMNB1 and LMNB2 are prognostic factors for HCC. GSK461364 is a novel therapeutic candidate for HCC, with anti-HCC effects associated with LMNB1/2 suppression.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligustilide Inhibits the PI3K/AKT Signalling Pathway and Suppresses Cholangiocarcinoma Cell Proliferation, Migration, and Invasion.","authors":"Yue Wu, Li Rong, Suifeng Zhang, Yuxi He, Na Song, Guoqing Zuo, Zhechuan Mei","doi":"10.2174/0115748928332384240812060751","DOIUrl":"10.2174/0115748928332384240812060751","url":null,"abstract":"<p><strong>Background: </strong><i>Angelica sinensis</i> (Oliv.) Diels, a renowned traditional Chinese medicine, has gained widespread recognition for its antitumor properties. Further investigation is warranted to determine whether ligustilide (LIG), which is extracted from this plant, can effectively inhibit tumors.</p><p><strong>Objectives: </strong>We delved into the impact of LIG on cholangiocarcinoma cells, aiming to unravel the mechanisms underlying its effects.</p><p><strong>Materials and methods: </strong>Cholangiocarcinoma cells (HuccT1 and RBE) were exposed to varying concentrations of LIG (2, 5, 10, 15, 20 μg/mL) for 24, 48, and 72 h. After identifying differentially expressed genes, stable transcription strains were utilized to explore LIG's antitumor mechanism. The inhibitory effects of LIG (5 μg/mL, 48 h) were assessed by CCK-8, colony formation, wound healing, transwell migration, western blotting, and immunofluorescence. <i>In vivo</i>, experiments in NOG mice (Ac, Ac+LIG; five per group) evaluated LIG's antiproliferative efficacy (5 mg/kg, intraperitoneal injection, 18-day period).</p><p><strong>Results: </strong>LIG significantly inhibited cell proliferation and migration with IC₅₀ 5.08 and 5.77 μg/mL in HuccT1 and RBE cell lines at 48h, increased the expression of E-cadherin while decreased N-cadherin and the protein of PI3K/AKT pathway. Silenced NDRG1 (N-Myc downstream- regulated gene 1) attenuated these effects. <i>In vivo</i>, the AC+LIG group (LIG, 5 mg/kg, qd, 18 d) exhibited smaller tumor volumes compared to the Ac group. The expression of Ki-67 was significantly downregulated in the AC+LIG group.</p><p><strong>Conclusion: </strong>For the first time, our study has revealed that LIG holds therapeutic potential for treating cholangiocarcinoma. These findings hold promise for advancing innovative therapeutic approaches in the treatment of cholangiocarcinoma. LIG may serve as a useful patent for treating CCA.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"200-212"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The m⁶A Reader IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression by Maintaining UCA1 Stability.","authors":"Duheyi Zhang, Lianxi Mai, Lizao Zhang, Guoxin Huang, Zhaoyu Lin, Shuang Wang, Guangxin Rao, Shule Xie, Chaobin Pan","doi":"10.2174/0115748928293003240817180839","DOIUrl":"10.2174/0115748928293003240817180839","url":null,"abstract":"<p><strong>Introduction: </strong>N6-methyladenosine (m⁶A) modifications of RNAs are associated with many cancer types. Nevertheless, the function of the m⁶A reader IGF2BP2 in oral squamous cell carcinoma (OSCC) has yet to be ascertained.</p><p><strong>Aims: </strong>The objective of this investigation was to elucidate the role of IGF2BP2 in OSCC and delineate the associated mechanisms.</p><p><strong>Methods: </strong>Elevated expression of IGF2BP2 was observed in OSCC, and this overexpression significantly correlated with adverse prognostic outcomes in patients with OSCC. In vitro analyses demonstrated that silencing of IGF2BP2 attenuated the proliferation, migration, and invasion capabilities of oral cancer cells while concurrently promoting apoptosis.</p><p><strong>Results: </strong>In vivo experiments demonstrated that IGF2BP2 promoted OSCC growth. RNA-seq and m⁶A-seq were utilized to elucidate the downstream targets of IGF2BP2. Through bioinformatic analysis, we identified the long noncoding RNA (lncRNA) UCA1 as a target. IGF2BP2 was found to maintain the stability of UCA1 in an m⁶A-dependent manner by binding to m⁶A-modified UCA1 and plays an oncogenic role in OSCC through UCA1.</p><p><strong>Conclusion: </strong>In conclusion, we identified IGF2BP2 as a prognostic biomarker of OSCC, and the IGF2BP2-UCA1 axis was found to promote OSCC progression and may perform as a novel therapeutic target.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"697-709"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Refractory p53 Mutation Large B-cell Lymphoma with Daratumumab and Venetoclax Followed by CAR-T Cell Therapy: Case Report and Animal Study.","authors":"Duanhao Gong, Jia Gu, Kuangguo Zhou, Wei Huang","doi":"10.2174/0115748928273058231128073414","DOIUrl":"10.2174/0115748928273058231128073414","url":null,"abstract":"<p><strong>Background: </strong>The tumor burden before chimeric antigen receptor T (CAR-T) cell therapy was one of the critical factors affecting the prognosis of lymphoma. It was a challenge to effectively reduce the tumor burden of relapsed/refractory large B-cell lymphoma with p53 mutation.</p><p><strong>Objective: </strong>Here, we have presented a case of relapsed/refractory large B-cell lymphoma with p53 mutation being controlled by the treatment with daratumumab and venetoclax, followed by CAR-T cell therapy.</p><p><strong>Case presentation: </strong>The patient was a 56-year-old female who was diagnosed with relapsed/ refractory diffuse large B cell lymphoma (DLBCL) transformed from follicular lymphoma. The patient was treated with daratumumab, venetoclax, and GEMOX (gemcitabine and oxaliplatin) under the guidance of high-throughput drug sensitivity analysis. We used a CD38 positive lymphoma cell line with p53 mutation to construct tumor models for validating the anti- lymphoma effect of the combination therapy of daratumumab and venetoclax.</p><p><strong>Results: </strong>The patient achieved a complete metabolic response after treatment with daratumumab, venetoclax, and GEMOX. Then, she further achieved a complete molecular response after she subsequently received CAR-T cell therapy, and she has been living without a lymphoma recurrence. The results from the animal study showed that the combination of daratumumab and venetoclax could significantly enhance the antitumor effect on CD38-positive lymphoma with p53 mutation.</p><p><strong>Conclusion: </strong>The results from our successful case and animal experiments provide new avenues for the treatment of relapsed/refractory large B-cell lymphoma with p53 mutation. Further clinical trials are reuqired to treat CD38-positive lymphoma with the combination of daratumumab and venetoclax.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"513-519"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies.","authors":"Bosheng Zheng, Wenqi Zhang, Shaonan Xie, Yaqing Han, Guangjie Liu, Yanjie Liu, Maogang Gao, Shize Wang, Qingyi Liu","doi":"10.2174/0115748928322627241016120142","DOIUrl":"10.2174/0115748928322627241016120142","url":null,"abstract":"<p><p>Selinexor treats lung cancer, particularly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). This review summarizes the prevalence and types of lung cancer and emphasizes the challenges associated with current treatments like resistance and limited effectiveness. Selinexor is a selective inhibitor of nuclear export (SINE) that has emerged as a potential therapy that targets the nuclear export of tumor suppressor proteins. The mechanisms of selinexor, its potential in combination therapies, and challenges like side effects and drug resistance are explained in this review. Key findings highlight the effectiveness of selinexor in preclinical studies, particularly against KRAS-mutant NSCLC and in combination with chemotherapy for SCLC. The review concludes with a discussion of future directions and underscores the potential of selinexor to improve the treatment strategies for lung cancer.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"274-284"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased SLC7A3 Expression Inhibits Tumor Cell Proliferation and Predicts a Favorable Prognosis in Breast Cancer.","authors":"Lifang He, Yue Xu, Jiediao Lin, Stanley Li Lin, Yukun Cui","doi":"10.2174/0115748928279007231130070056","DOIUrl":"10.2174/0115748928279007231130070056","url":null,"abstract":"<p><strong>Background: </strong>Arginine plays significant and contrasting roles in breast cancer growth and survival. However, the factors governing arginine balance remain poorly characterized.</p><p><strong>Objective: </strong>We aimed to identify the molecule that governs arginine metabolism in breast cancer and to elucidate its significance.</p><p><strong>Methods: </strong>We analyzed the correlation between the expression of solute carrier family 7 member 3 (SLC7A3), the major arginine transporter, and breast cancer survival in various databases, including GEPIA, UALCAN, Metascape, String, Oncomine, KM-plotter, CBioPortal and PrognoScan databases. Additionally, we validated our findings through bioinformatic analyses and experimental investigations, including colony formation, wound healing, transwell, and mammosphere formation assays.</p><p><strong>Results: </strong>Our analysis revealed a significant reduction in SLC7A3 expression in all breast cancer subtypes compared to adjacent breast tissues. Kaplan-Meier survival analyses demonstrated that high SLC7A3 expression was positively associated with decreased nodal metastasis (HR=0.70, 95% CI [0.55, 0.89]), ER positivity (HR=0.79, 95% CI [0.65, 0.95]), and HER2 negativity (HR=0.69, 95% CI [0.58, 0.82]), and increased recurrence-free survival. Moreover, low SLC7A3 expression predicted poor prognosis in breast cancer patients for overall survival. Additionally, the knockdown of SLC7A3 in MCF-7 and MDA-MB-231 cells resulted in increased cell proliferation and invasion <i>in vitro</i>.</p><p><strong>Conclusion: </strong>Our findings indicate a downregulation of SLC7A3 expression in breast cancer tissues compared to adjacent breast tissues. High SLC7A3 expression could serve as a prognostic indicator for favorable outcomes in breast cancer patients due to its inhibitory effects on breast cancer cell proliferation and invasion.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"55-70"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adhesin Component Member STAG2 Enhances Cisplatin Tolerance in Colorectal Cancer Cells through the Epithelial-mesenchymal Transition Pathway.","authors":"Pengjun Zhou, Meiyi Ye, Chunlan Chen, Rong Zhang","doi":"10.2174/0115748928305100240613064754","DOIUrl":"10.2174/0115748928305100240613064754","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Platinum-based compounds are commonly used as an initial treatment for colorectal cancer (CRC). However, the development of drug resistance in patients with CRC necessitates the administration of high drug concentrations during clinical treatment, thereby augmenting the toxicity of platinum-based compounds and increasing the mortality rate. STAG2 is a significantly associated drug-resistance gene in many cancers, but it has not been studied in colorectal cancer. Therefore, the present study aimed to investigate the role and drug sensitivity of the cisplatin-resistant gene STAG2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The effects of STAG2 on drug resistance and survival rates of patients with CRC were examined using the Genomics of Drug Sensitivity in Cancer (GDSC) and Kaplan-Meier (KM) plotter databases. Subsequently, a sh-STAG2-HT-29 cell line was generated using a knockdown test of STAG2, and the half-maximal inhibitory concentration (IC50) of the two cell lines was determined using a cell viability test. We then used various techniques, including the Cell Counting Kit-8 (CCK-8), plate cloning, 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining, flow cytometry for cell cycle detection, the scar assay, the Transwell invasion assay, and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) fluorescence staining for apoptosis detection, to investigate the functionality of the four subgroups of cancer cell lines. Additionally, Western blotting (WB) was used to identify the potential pathways associated with the observed functional alterations. Finally, the phenotype, tumor weight, mouse weight, tumor volume, and tumor tissue structure of the developed tumors were assessed using the subcutaneous tumor formation method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Database analysis indicated that STAG2 plays a role in facilitating drug resistance among individuals with CRC. Furthermore, mutations in this gene lead to increased sensitivity to cisplatin, and its overexpression was associated with an unfavorable prognosis. Following the successful development of STAG2 knockdown cells, differences in IC50 concentrations were observed between HT-29 and sh-STAG2-HT-29 cells. A treatment concentration of 10 μM cisplatin was selected, and the proliferation, migration, and invasion capabilities of cancer cells decreased after STAG2 knockdown. Additionally, the sensitivity of the cells to cisplatin therapy was increased, which was potentially mediated by the epithelial-mesenchymal transition (EMT) pathway. In mice, the tumorigenic potential of HT-29 cells was reduced by STAG2 knockdown, accompanied by a decrease in resistance to cisplatin therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;STAG2 acts as a proto-oncogene in CRC, and its resistance to cisplatin therapy is more prominent. This study confirmed the role of STAG2 in CRC and provided a theoretical basis for the further development of STAG2 as an auxiliary criterion for determining ","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"741-752"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Role of ADAM 12 Regulates Epithelial-mesenchymal Transition by Activating the Wnt/β-catenin Signaling Pathway in Colorectal Cancer.","authors":"Chengchen Huang, Jian Wang, Jianqin Xiang, Chunrong Wu, Fan Wang, Jiangyan Chen, Guiyin Sun, Debing Xiang","doi":"10.2174/0115748928305105240417101251","DOIUrl":"10.2174/0115748928305105240417101251","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to investigate the expression and regulatory mechanisms of A disintegrin and metalloproteinase domain 12 (ADAM12) in colorectal cancer (CRC) tissues and cells.</p><p><strong>Methods: </strong>Download and analyze the expression levels of ADAM12 in the TCGA and GSE68468 datasets. Collect paraffin-preserved specimens from the Chongqing University Jiangjin Hospital from April 2017 to December 2019 and detect the expression of ADAM12 through immunohistochemistry. Cell experiments were conducted using colorectal cancer cell lines (SW480, HCT116), and cells with high expression of ADAM12 were selected for silencing experiments, and cell proliferation ability using CCK-8, and migration ability of cells in each group using scratch assay and Transwell invasion assay. The EMT markers (E-cadherin, N-cadherin, Vimentin, Twist) and the Wnt/β-catenin markers (β-catenin, GSK-3β, p-GSK-3β, C-MYC, MMP-7) were detected using western blot. We construct a nude mouse CRC tumor model and validate the effect of ADAM12 on EMT and Wnt/β-catenin through immunohistochemistry and Western blot.</p><p><strong>Results: </strong>Bioinformatics showed that increased expression of ADAM12 was strongly correlated with patient prognosis. Immunohistochemistry showed that elevated ADAM12 was associated with vascular invasion (p < 0.05), neurological invasion (p < 0.01), lymph node metastasis (p < 0.01), and TNM staging (p < 0.001). Experiments on cell function revealed that the ADAM12 overexpression group augmented CRC cells' proliferation and migration. After overexpression of ADAM12, the expression of N-cadherin, Vimentin, and Twist increased, while the expression of E-cadherin decreased (p < 0.01). The expression of Proteins related to Wnt/β-catenin: β-catenin, p-GSK-3 β, C-MYC and MMP-7 increased (p < 0.01), and Wnt/β-catenin inhibitor MSAB can counteract the effect of ADAM12 on EMT in CRC cells. The subcutaneous tumor formation experiment results in nude mice showed that ADAM12 promoted tumor growth and induced EMT compared to the control group.</p><p><strong>Conclusion: </strong>ADAM12 overexpression through the Wnt/β-catenin signal axis controls the EMT of CRC to promote invasion and metastasis.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"248-259"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140878253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UBE2L3 Suppresses Oxidative Stress-regulated Necroptosis to Accelerate Osteosarcoma Progression.","authors":"Xiwu Zhao, Guoqiang Shan, Deguo Xing, Hongwei Gao, Zhenggang Xiong, Wenpeng Hui, Mingzhi Gong","doi":"10.2174/0115748928297557240212112531","DOIUrl":"10.2174/0115748928297557240212112531","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma is a highly invasive bone marrow stromal tumor with limited treatment options. Oxidative stress plays a crucial role in the development and progression of tumors, but the underlying regulatory mechanisms are not fully understood. Recent studies have revealed the significant involvement of UBE2L3 in oxidative stress, but its specific role in osteosarcoma remains poorly investigated.</p><p><strong>Objective: </strong>This study aimed to explore the molecular mechanisms by which UBE2L3 promotes oxidative stress-regulated necroptosis to accelerate the progression of osteosarcoma using in vitro cell experiments.</p><p><strong>Methods: </strong>Human osteoblast hFOB1.19 cells and various human osteosarcoma cell lines (MG-63, U2OS, SJSA-1, HOS, and 143B) were cultured in vitro. Plasmids silencing UBE2L3 and negative control plasmids were transfected into U2OS and HOS cells. The cells were divided into the following groups: U2OS cell group, HOS cell group, si-NC-U2OS cell group, si-UBE2L3-U2OS cell group, si-NC-HOS cell group, and si-UBE2L3-HOS cell group. Cell viability and proliferation capacity were measured using the Tunnel method and clonogenic assay. Cell migration and invasion abilities were assessed by Transwell and scratch assays. Cell apoptosis was analyzed by flow cytometry, and ROS levels were detected using immunofluorescence. The oxidative stress levels in various cell groups and the expression changes of necroptosis-related proteins were assessed by PCR and WB. Through these experiments, we aim to evaluate the impact of oxidative stress on necroptosis and uncover the specific mechanisms by which targeted regulation of oxidative stress promotes tumor cell necroptosis as a potential therapeutic strategy for osteosarcoma.</p><p><strong>Results: </strong>The mRNA expression levels of UBE2L3 in human osteosarcoma cell lines were significantly higher than those in human osteoblast hFOB1.19 cells (p <0.01). UBE2L3 expression was significantly decreased in U2OS and HOS cells transfected with si-UBE2L3, indicating the successful construction of stable cell lines with depleted UBE2L3. Tunnel assay results showed a significant increase in the number of red fluorescent-labeled cells in si-UBE2L3 groups compared to si-NC groups in both cell lines, suggesting a pronounced inhibition of cell viability. Transwell assay demonstrated a significant reduction in invasion and migration capabilities of si-UBE2L3 groups in osteosarcoma cells. The clonogenic assay revealed significant suppression of proliferation and clonogenic ability in both U2OS and HOS cells upon UBE2L3 knockdown. Flow cytometry confirmed that UBE2L3 knockdown significantly enhanced apoptosis in U2OS and HOS cells. Immunofluorescence results showed that UBE2L3 silencing promoted oxidative stress levels in osteosarcoma cells and facilitated tumor cell death. WB analysis indicated a significant increase in phosphorylation levels of necroptosis-relate","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"102-112"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organosulfur Compounds in Garlic for Gastric Cancer Treatment: Anticancer Effects, Overcoming Drug Resistance, and Mechanisms.","authors":"Xudong Yi, Jinrui Zhang, Yiman Yao, Junyu Liu, Mingyue Li, Min Zhang, Anat Elmann, Haixia Chen","doi":"10.2174/0115748928367900250116074925","DOIUrl":"10.2174/0115748928367900250116074925","url":null,"abstract":"<p><p>Garlic (Allium sativum L.) has been consumed globally as a functional food and traditional medicine for various ailments. Its active organosulfur compounds (OSCs) have demonstrated significant anticancer properties, particularly against gastric cancer. However, a comprehensive review of these effects and the underlying molecular mechanisms, including their role in overcoming drug resistance, is currently lacking. This review systematically examines both preclinical and clinical studies on the anticancer effects of garlic and its organosulfur compounds against gastric cancer, with a focus on patents. Emphasis is placed on explaining the mechanisms of action, exploring how these compounds can overcome drug resistance, and highlighting relevant patents that have been granted in this field. The literature search included databases, like PubMed, Web of Science, Google Scholar, ScienceDirect, and patent databases, including articles and patents published up to October 2024. Preclinical studies demonstrate that garlic-derived organosulfur compounds possess anticancer activities against gastric cancer. They work through multiple mechanisms, including inducing apoptosis, causing cell cycle arrest, inhibiting cancer stem cell properties, suppressing epithelial-mesenchymal transition, and modulating key signaling pathways, like PI3K/Akt and NF-κB. These compounds also show potential in overcoming drug resistance by downregulating multidrug resistance proteins and enhancing the effectiveness of standard chemotherapy drugs. Clinical studies suggest that regular garlic consumption may reduce the risk of gastric cancer and improve outcomes in patients undergoing chemotherapy. This review highlights the significant potential of garlic's organosulfur compounds as complementary agents in gastric cancer prevention and treatment and emphasizes the relevance of existing patents and the need for further clinical trials to confirm these effects and develop effective therapeutic strategies.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"306-318"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}