Recent patents on anti-cancer drug discovery最新文献

{"title":"Structure-Based Virtual Screening Identifying Novel FOXM1 Inhibitors as the Lead Compounds for Glioblastoma","authors":"Kumari Swati, Rashi Srivastava, Kirti Agrawal, Siva Prasad Panda, Anand Parkash, Dhruv Kumar, Hailiang Chen","doi":"10.2174/0115748928289164240426110829","DOIUrl":"https://doi.org/10.2174/0115748928289164240426110829","url":null,"abstract":"Background: Glioblastoma multiforme (GBM) is a highly heterogeneous brain tumor with limited treatment options and a poor prognosis. Cancer stem cells (CSCs) have emerged as a critical factor in GBM resistance and management, contributing to tumor growth, heterogeneity, and immunosuppression. The transcription factor FOXM1 has been identified as a key player in the progression, spread, and therapy resistance of various cancers, including GBM. Objective: In this research, the objective was to perform structure-based in silico screening with the aim of identifying natural compounds proficient in targeting the DNA-binding domain (DBD) of the FOXM1 protein. Methods: In this study, in silico tools were employed for screening a hundred naturally occurring compounds capable of targeting the FOXM1 protein. Through molecular docking analysis and pharmacokinetic profiling, five compounds were found to be promising candidates for extensive interaction with the FOXM1 protein. Further, these compounds were validated for the stability of the FOXM1-natural compound complex using molecular dynamics (MD) simulations. Results: Four compounds, such as Withaferin A, Bryophyllin A, Silybin B, Sanguinarine and Troglitazone (control compound), emerged as promising candidates with substantial interactions with FOXM1, suggesting their potential as a protein inhibitor based on molecular docking investigations. After MD simulation analysis, the FOXM1- Bryophyllin A complex was found to maintain the highest stability, and the other three ligands had moderate but comparable binding affinities over a period of 100 ns. Conclusion: This study provides valuable insights into four promising FOXM1 inhibitors that have the ability to induce senescence in GBM stem cells. These findings contribute to the development of structure-based designing strategies for FOXM1 inhibitors and innovative therapeutic approaches for the treatment of Glioblastoma.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"34 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Prognostic Risk Model Based on Oxidative StressRelated Genes for Platinum-Resistant Ovarian Cancer Patients","authors":"Huishan Su, Yaxin Hou, Difan Zhu, Rongqing Pang, Shiyun Tian, Ran Ding, Ying Chen, Sihe Zhang","doi":"10.2174/0115748928311077240424065832","DOIUrl":"https://doi.org/10.2174/0115748928311077240424065832","url":null,"abstract":"Introduction: Ovarian Cancer (OC) is a heterogeneous malignancy with poor outcomes. Oxidative stress plays a crucial role in developing drug resistance. However, the relationships between Oxidative Stress-related Genes (OSRGs) and the prognosis of platinum-resistant OC remain unclear. This study aimed to develop an OSRGs-based prognostic risk model for platinum-resistant OC patients. Methods: Gene Set Enrichment Analysis (GSEA) was performed to determine the expression difference of OSRGs between platinum-resistant and -sensitive OC patients. Cox regression analyses were used to identify the prognostic OSRGs and establish a risk score model. The model was validated by using an external dataset. Machine learning was used to determine the prognostic OSRGs associated with platinum resistance. Finally, the biological functions of selected OSRG were determined via in vitro cellular experiments. Results: Three gene sets associated with oxidative stress-related pathways were enriched (p < 0.05), and 105 OSRGs were found to be differentially expressed between platinum-resistant and - sensitive OC (p < 0.05). Twenty prognosis-associated OSRGs were identified (HR: 0:562-5.437; 95% CI: 0.319-20.148; p < 0.005), and seven independent OSRGs were used to construct a prognostic risk score model, which accurately predicted the survival of OC patients (1-, 3-, and 5-year AUC=0.69, 0.75, and 0.67, respectively). The prognostic potential of this model was confirmed in the validation cohort. Machine learning showed five prognostic OSRGs (SPHK1, PXDNL, C1QA, WRN, and SETX) to be strongly correlated with platinum resistance in OC patients. Cellular experiments showed that WRN significantly promoted the malignancy and platinum resistance of OC cells. Conclusion: The OSRGs-based risk score model can efficiently predict the prognosis and platinum resistance of OC patients. This model may improve the risk stratification of OC patients in the clinic.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"37 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cell Markers in Neoplasms and their Relationship with Progression-free and Overall Survival in Patients with Recurrence","authors":"Aldo Eguiluz-Melendez, Carmen Rubio-Osornio, Artemio Rosiles-Abonce, Cesar Mendoza, Miryam Ramírez-Ordás, Romina Rivera-Cañas, Martha Tena-Suck, Juan Luis Gómez-Amador, Sergio Moreno-Jimenez","doi":"10.2174/0115748928277672240429065526","DOIUrl":"https://doi.org/10.2174/0115748928277672240429065526","url":null,"abstract":"Background: Gliomas account for 30% of primary brain tumors in adults, and despite the scientific progress in the field, recurrence is prevalent. Glioma Stem Cells (GSCs) can generate tumor cells in vivo and in vitro and they are associated with treatment resistance, tumor progression, and recurrence. Furthermore, the expression of SOX transcription factors (SOX1, SOX2, SOX9) in these cells is responsible for maintaining an oncogenic genotype and is associated with an aggressive tumor phenotype. The relationship between SOX transcription factors and their prognostic role in recurrent gliomas has not been described in detail. Therefore, we set out to describe the relationship between SOX expression and Progression-free Survival (PFS) and Overall Survival (OS) in patients with recurrent gliomas. Methods: In this observational study, we have retrospectively analyzed 69 patients, of which 20 met the inclusion criteria. The clinical, radiological, and histopathological findings have been described, and survival analysis has been performed according to SOX expression for PFS and OS. Results: We found SOX1, SOX2, and SOX9 to show a non-statistically significant trend with increasing histopathological grade, co-expressed with Ki67, a cell proliferation factor. Conclusion: There has been found an inversely proportional correlation between the degree of immunopositivity of SOX1 and OS. A higher SOX1 immunopositivity could predict a worse clinical prognosis. There has also been found an interaction between a pluripotent genotype (GSC) and cell proliferation.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"155 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140942158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sema3A Inhibits Osteolytic Bone Metastasis of Non-small Cell Lung Cancer","authors":"Wei Wang, Kaicheng Shen, Ruyan Liu, Qi Zhou","doi":"10.2174/0115748928295263240402085411","DOIUrl":"https://doi.org/10.2174/0115748928295263240402085411","url":null,"abstract":"Background: Osteolytic bone metastasis is a common complication of Non-Small Cell Lung Cancer (NSCLC), resulting in bone pain, hypercalcemia, and fractures that severely reduce the quality of life and survival time of patients. Semaphorins 3A (Sema3A) is one of the isoforms of the Semaphorins family, which is important in a variety of physiological and pathological processes, such as angiogenesis, immune regulation, and tumorigenesis. However, the role of Sema3A in the development of osteolytic bone metastasis in NSCLC is unknown. Methods: In this study, we established in vitro models simulating NSCLC cells in regulating the differentiation and maturation of osteoblast and osteoclast precursors and observed the differentiation of osteoblasts and osteoclasts. Results: The results demonstrated that the expression of Sema3A inhibited the proliferation, migration, and invasion of NSCLC cells, as well as promoted the differentiation of osteoblasts and inhibited the differentiation of osteoclasts, suggesting that Sema3A can inhibit the occurrence and development of osteolytic bone metastasis of NSCLC. Conclusion: This study provides a new idea for the clinical treatment of osteolytic bone metastasis in NSCLC.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"4 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140617664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eukaryotic Initiation Factor 3C Can Affect the Proliferation and Invasion of Ovarian Cancer by Regulating the p53 Signalling Pathway","authors":"Jingkaiwen Zhang, Hanlin Yang, Fang Wen, Qing Li, Hao Luo, Dan Zi","doi":"10.2174/0115748928292248240401051408","DOIUrl":"https://doi.org/10.2174/0115748928292248240401051408","url":null,"abstract":"Background: Eukaryotic Initiation Factor 3C (EIF3C) represents a pivotal translational initiation factor in eukaryotes and has been shown to facilitate the progression of various neoplasms. However, its mechanistic role in ovarian cancer remains elusive. Methods: In this research, the expression of EIF3C in ovarian cancer tissues was investigated using immunohistochemistry. In addition, the assessments were made on changes in cellular proliferation, invasion, and apoptotic abilities by reducing the expression of EIF3C in ovarian cancer cells. By utilizing microarray analysis, a comparison was performed between the downregulated EIF3C group and the control group of ovarian cancer cells, revealing the genes that were expressed differently. Furthermore, the signalling pathways associated with cellular proliferation were validated. The functional role of EIF3C in vivo was investigated using a xenograft tumour model. Results: The immunohistochemical analysis showed that elevated levels of EIF3C are linked to a negative prognosis in patients with ovarian cancer. Suppression of EIF3C greatly hindered the growth and spread of SK-OV-3 and HO-8910 cells while enhancing cellular programmed cell death. Following KEGG and GSEA enrichment analyses of differentially expressed genes, the p53 signalling pathway was found to be associated with EIF3C. Suppression of EIF3C resulted in the upregulation of the p53 signalling pathway, leading to the inhibition of cell proliferation and invasion and the promotion of apoptosis. In vivo experiments demonstrated that EIF3C knockdown suppressed the growth of subcutaneous tumours in nude mice. Conclusion: There is a correlation between overexpression of EIF3C in tumour tissues of ovarian cancer patients and this is associated with a poorer prognosis. By influencing the p53 signaling pathway, EIF3C facilitates the growth and infiltration of cells in ovarian cancer.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"306 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fat-soluble Vitamins and Lung Cancer: Where We Are?","authors":"Xue Lin, Yaxuan Wang, Tongzuo Zhang, Xiaoyan Pu","doi":"10.2174/0115748928283728240320063619","DOIUrl":"https://doi.org/10.2174/0115748928283728240320063619","url":null,"abstract":": Fat-soluble vitamins (vitamins A, D, E, and K) are vital substances for maintaining normal physiological functions in the body. In recent years, scholars have explored the relationship between fat-soluble vitamins and the wasting disease - lung cancer. In this paper, we review recent studies on fat-soluble vitamins and lung cancer to clarify the relevance and molecular mechanisms of various vitamins in lung cancer, and whether the levels of fat-soluble vitamins in the body and vitamin supplementation affect the development of lung cancer. Our review could facilitate the discovery of biomarkers, potential therapeutic targets in lung cancer, and anti-tumor adjuvant drugs, in addition to highlighting other new ideas in the prevention and treatment of lung cancer.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140562330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis","authors":"Xinglan He, Guanyu Wang, Yimeng Wang, Chunlei Zhang","doi":"10.2174/0115748928289036240318040756","DOIUrl":"https://doi.org/10.2174/0115748928289036240318040756","url":null,"abstract":"Background: Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. Methods: Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 μmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. Results and Discussion: Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. Conclusion: Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"240 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140562452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic Analysis and Experimental Validation of HMGA2-AS1 as a Prognostic Biomarker Associated with Immune Infiltration in Gastric Cancer","authors":"Guizhen Lyu","doi":"10.2174/0115748928284459240318070914","DOIUrl":"https://doi.org/10.2174/0115748928284459240318070914","url":null,"abstract":"Background: Natural antisense long noncoding RNAs (lncRNAs) have the ability to modulate the expression of their corresponding sense genes. Consequently, any dysregulation of these lncRNAs can contribute to the development of pathological processes. The ambiguity surrounding the role of HMGA2-AS1 in gastric cancer (GC) requires further investigation. Objective: The aim of this study was to examine the involvement of HMGA2-AS1 in GC. Methods: The Kaplan-Meier method, Cox regression analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis were used in this study. These methods were used to evaluate the relationship between clinical characteristics and HMGA2-AS1 expression, prognostic factors, and the significant functional impact of HMGA2-AS1. HMGA2-AS1 levels in GC cell lines were validated using quantitative real-time polymerase chain reaction (qRT-PCR). Results: In patients diagnosed with GC, a significant correlation was observed between high expression of HMGA2-AS1 and the T stage (p = 0.01). Furthermore, the high expression of HMGA2- AS1 was identified as a prognostic indicator for poorer OS (p = 0.004), PFS (p = 0.006), and DSS (p = 0.011). Furthermore, the expression of HMGA2-AS1 (p < 0.001) demonstrated an independent association with OS in patients with GC. The presence of a low expression phenotype of HMGA2-AS1 was associated with differential enrichment of various pathways, including the focal adhesion-PI3K-Akt-mTOR signaling pathway, focal adhesion, ECM glycoproteins, MET promoting cell motility, among others. Furthermore, the expression of HMGA2-AS1 exhibited correlations with B cells, CD56 bright cells, and TFH and Th17 cells. Furthermore, GC cell lines demonstrated significantly higher expression of HMGA2-AS1. Conclusion: Elevated expression of HMGA2-AS1 in GC patients exhibited a significant correlation with unfavorable survival outcomes and increased immune infiltration. This suggests that HMGA2- AS1 holds promise as a potential prognostic biomarker and target for immunotherapy in GC.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"27 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140562362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulating Lipid Metabolism via Mitochondrial Dynamics in Tongue Squamous Cell Carcinoma Cancer Stem Cells","authors":"Fan Wu, Suling Chen, Siqi Ren, Ruixin Wang, Yongmei Tan, Rongxi Chen, Bowen Li, Haotian Cao, Jinsong Li","doi":"10.2174/0115748928275772231226063458","DOIUrl":"https://doi.org/10.2174/0115748928275772231226063458","url":null,"abstract":"Background: Cancer stem cells (CSCs) are a sub-population of cancer cells present in many kinds of malignant tumors that have the potential for self-proliferation and differentiation. These cells have been demonstrated as the main cause of tumor recurrence and metastasis. Strong evidence indicates that CSCs prefer reprogrammed fatty acid β-oxidation over oxidative phosphorylation for sustaining energy supply. Although mitochondrial dynamics participate in the regulation of cancer stemness, the correlation between the inhibition of mitochondrial fission and the regulation of lipid metabolism in CSCs remains poorly understood. Methods: The human tongue squamous cell carcinoma (TSCC) cell lines CAL27 and SAS were used to obtain the CSCs by 3D Spheroid Culture. Then,western blot methods, RT-PCR and flow cytometry analysis were used to identify the TSCC CSCs. Next, Immunofluorescence method, transmission electron microscopy detection and western blot methods were used to evaluate the mitochondrial morphology and the quantity of lipid droplets (LDs). Lastly, lipidomic analysis was applied to explored the lipidomic alterations of TSCC CSCs with different mitochondrial morphology. Results: Here, we show that the quantity of lipid droplets containing intracellular triglyceride (TG) can be decreased by regulating mitochondrial morphology. Lipidomic analysis using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) also compared alterations in lipid metabolites in tongue squamous cell carcinoma (TSCC) CSCs, TSCC cells (non-CSCs), and CSCs with different mitochondrial morphology. Discriminant lipids of statistical significance were successfully annotated, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), sphingomyelins (SMs), triacylglycerols (TGs), phosphatidylglycerols (PGs), phosphatidylserines (PSs), lysophosphatidylcholines (LPCs), and lysophosphatidylethanolamines (LPEs). Conclusion: This study provides a deeper insight into the alterations of lipid metabolism associated with TSCC CSCs, non-CSCs and CSCs regulated by mitochondrial dynamics and thus serves as a guide toward novel targeted therapies.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"14 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139666889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SSPH I, A Novel Anti-cancer Saponin, Inhibits EMT and Invasion and Migration of NSCLC by Suppressing MAPK/ERK1/2 and PI3K/AKT/mTOR Signaling Pathways","authors":"Jinling Zhou, Jian Luo, Rizhi Gan, Limin Zhi, Huan Zhou, Meixian Lv, Yinmei Huang, Gang Liang","doi":"10.2174/0115748928283132240103073039","DOIUrl":"https://doi.org/10.2174/0115748928283132240103073039","url":null,"abstract":"Background: Saponin of Schizocapsa plantaginea Hance I (SSPH I)，a bioactive saponin found in Schizocapsa plantaginea, exhibits significant anti-proliferation and antimetastasis in lung cancer. Objective: To explore the anti-metastatic effects of SSPH I on non-small cell lung cancer (NSCLC) with emphasis on epithelial-mesenchymal transition (EMT) both in vitro and vivo. Methods: The effects of SSPH I at the concentrations of 0, 0.875,1.75, and 3.5 μM on A549 and PC9 lung cancer cells were evaluated using colony formation assay, CCK-8 assay, transwell assay and wound-healing assay. The actin cytoskeleton reorganization of PC9 and A549 cells was detected using the FITC-phalloidin fluorescence staining assay. The proteins related to EMT (N-cadherin, E-cadherin and vimentin), p- PI3K, p- AKT, p- mTOR and p- ERK1/2 were detected by Western blotting. A mouse model of lung cancer metastasis was established by utilizing 95-D cells, and the mice were treated with SSPH I by gavage. Results: The results suggested that SSPH I significantly inhibited the migration and invasion of NSCLC cells under a non-cytotoxic concentration. Furthermore, SSPH I at a non-toxic concentration of 0.875 μM inhibited F-actin cytoskeleton organization. Importantly, attenuation of EMT was observed in A549 cells with upregulation in the expression of epithelial cell marker E-cadherin and downregulation of the mesenchymal cell markers vimentin as well as Ncadherin. Mechanistic studies revealed that SSPH I inhibited MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways. Conclusion: SSPH I inhibited EMT, migration, and invasion of NSCLC cells by suppressing MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways, suggesting that the natural compound SSPH I could be used for inhibiting metastasis of NSCLC.","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"31 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139661915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}