{"title":"Identification of the Roles of Coagulation-related Signature and its Key Factor RABIF in Hepatoma Cell Malignancy.","authors":"Yanying Chen, Yin Li, Bingyi Zhou","doi":"10.2174/1574892819666230829151148","DOIUrl":"10.2174/1574892819666230829151148","url":null,"abstract":"<p><strong>Background: </strong>Hepatoma is a high morbidity and mortality cancer, and coagulation is a potential oncogenic mechanism for hepatoma development.</p><p><strong>Objective: </strong>In this study, we aimed to reveal the role of coagulation in hepatoma.</p><p><strong>Methods: </strong>We applied the LASSO to construct a coagulation-related risk score (CRS) and a clinical nomogram with independent validation. The heterogeneity of various aspects, including functional enrichment, SNV, CN, immunocyte infiltration, immune pathways, immune checkpoint, and genomic instability indexes, was evaluated. Besides, the prognostic value of the CRS genes was tested. We selected the critical risky gene related to coagulation from the LASSO coefficients, for which we applied transwell and clone formation assays to confirm its roles in hepatoma cell migration and clone formation ability, respectively.</p><p><strong>Results: </strong>The CRS and the nomogram predicted patients' survival with good accuracy in both two datasets. The high-CRS group was associated with higher cell cycle, DNA repair, TP53 mutation rates, amplification, and lower deletion rates at chromosome 1. For immunocyte infiltration, we noticed increased Treg infiltration and globally upregulated immune checkpoints and genomic instability indexes. Additionally, every single CRS gene affected the patient's survival. Finally, we observed that RABIF was the riskiest gene in the CRS. Its knockdown suppressed hepatoma cell migration and clone formation capability, which could be rescued by RABIF overexpression.</p><p><strong>Conclusion: </strong>We built a robust CRS with great potential as a prognosis and immunotherapeutic indicator. Importantly, we identified RABIF as an oncogene, promoting hepatoma cell migration and clone formation, revealing underlying pathological mechanisms, and providing novel therapeutic targets for hepatoma treatment.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"695-710"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10167660","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}
Yu-Yang Ma, Ge-Jin Zhang, Peng-Fei Liu, Ying Liu, Ji-Cun Ding, Hao Xu, Lin Hao, Deng Pan, Hai-Luo Wang, Jing-Kai Wang, Peng Xu, Zhen-Duo Shi, Kun Pang
{"title":"Comprehensive Genomic Analysis of Puerarin in Inhibiting Bladder Urothelial Carcinoma Cell Proliferation and Migration.","authors":"Yu-Yang Ma, Ge-Jin Zhang, Peng-Fei Liu, Ying Liu, Ji-Cun Ding, Hao Xu, Lin Hao, Deng Pan, Hai-Luo Wang, Jing-Kai Wang, Peng Xu, Zhen-Duo Shi, Kun Pang","doi":"10.2174/1574892819666230908110107","DOIUrl":"10.2174/1574892819666230908110107","url":null,"abstract":"<p><strong>Background: </strong>Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms.</p><p><strong>Methods: </strong>Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation.</p><p><strong>Results: </strong>A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218μmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients.</p><p><strong>Conclusion: </strong>Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"516-529"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10203838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Xiong, Zhenghe Chen, Chao Zhou, Xiaochun Yang, Wanming Hu, Yongluo Jiang, Rongliang Zheng, Wei Fan, Yonggao Mou, Xiaoping Lin
{"title":"PSMA PET/MR is a New Imaging Option for Identifying Glioma Recurrence and Predicting Prognosis.","authors":"Min Xiong, Zhenghe Chen, Chao Zhou, Xiaochun Yang, Wanming Hu, Yongluo Jiang, Rongliang Zheng, Wei Fan, Yonggao Mou, Xiaoping Lin","doi":"10.2174/1574892818666230519150401","DOIUrl":"10.2174/1574892818666230519150401","url":null,"abstract":"<p><strong>Background: </strong>Glioma is characterized by a high recurrence rate, while the results of the traditional imaging methods (including magnetic resonance imaging, MRI) to distinguish recurrence from treatment-related changes (TRCs) are poor. Prostate-specific membrane antigen (PSMA) (US10815200B2, Deutsches Krebsforschungszentrum, German Cancer Research Center) is a type II transmembrane glycoprotein overexpressed in glioma vascular endothelium, and it is a promising target for imaging and therapy.</p><p><strong>Objective: </strong>The study aimed to assess the performance of PSMA positron emission tomography/ magnetic resonance (PET/MR) for diagnosing recurrence and predicting prognosis in glioma patients.</p><p><strong>Materials and methods: </strong>Patients suspected of glioma recurrence who underwent <sup>18</sup>F-PSMA-1007 PET/MR were prospectively enrolled. Eight metabolic parameters and fifteen texture features of the lesion were extracted from PSMA PET/MR. The ability of PSMA PET/MR to diagnose glioma recurrence was investigated and compared with conventional MRI. The diagnostic agreement was assessed using Cohen κ scores and the predictive parameters of PSMA PET/MR were obtained. Kaplan-Meier method and Cox proportional hazard model were used to analyze recurrence- free survival (RFS) and overall survival (OS). Finally, the expression of PSMA was analyzed by immunohistochemistry (IHC).</p><p><strong>Results: </strong>Nineteen patients with a mean age of 48.11±15.72 were assessed. The maximum tumorto- parotid ratio (TPR<sub>max</sub>) and texture features extracted from PET and T1-weighted contrast enhancement (T1-CE) MR showed differences between recurrence and TRCs (all <i>p</i> <0.05). PSMA PET/MR and conventional MRI exhibited comparable power in diagnosing recurrence with specificity and PPV of 100%. The interobserver concordance was fair between the two modalities (<i>κ</i> = 0.542, <i>p</i> = 0.072). The optimal cutoffs of metabolic parameters, including standardized uptake value (SUV, SUV<sub>max</sub>, SUV<sub>mean</sub>, and SUV<sub>peak</sub>) and TPR<sub>max</sub> for predicting recurrence were 3.35, 1.73, 1.99, and 0.17 respectively, with the area under the curve (AUC) ranging from 0.767 to 0.817 (all <i>p</i> <0.05). In grade 4 glioblastoma (GBM) patients, SUV<sub>max</sub>, SUV<sub>mean</sub>, SUV<sub>peak</sub>, TBR<sub>max</sub>, TBR<sub>mean</sub>, and TPR<sub>max</sub> showed improved performance of AUC (0.833-0.867, <i>p</i> <0.05). Patients with SUVmax, SUVmean, or SUVpeak more than the cutoff value had significantly shorter RFS (all <i>p</i> <0.05). In addition, patients with SUVmean, SUVpeak, or TPR<sub>max</sub> more than the cutoff value had significantly shorter OS (all <i>p</i> <0.05). PSMA expression of glioma vascular endothelium was observed in ten (10/11, 90.9%) patients with moderate-to-high levels in all GBM cases (n = 6/6, 100%).</p><p><strong>Conclusion: </strong>This primitive study shows ","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"1 1","pages":"383-395"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41599003","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":"Fatty Acid Metabolism Signature Contributes to the Molecular Diagnosis of a Malignant Gastric Cancer Subtype with Poor Prognosis and Lower Mutation Burden.","authors":"Zhengwei Chen, Guoxiong Cheng","doi":"10.2174/1574892819666230907145036","DOIUrl":"10.2174/1574892819666230907145036","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a common gastrointestinal tumor with high morbidity and mortality. Fatty acid metabolism (FAM) contributes to GC development. Patents have been issued for the use of compositions comprising fatty acid analogues for the treatment of many clinical conditions. However, its clinical significance and its relationship with tumor-related mutations have not been thoroughly discovered. This study was conducted to analyze and explore FAM-related genes' molecular characteristics, prognostic significance, and association with tumor- related mutations.</p><p><strong>Methods: </strong>The gastric adenocarcinoma's transcriptome, clinical data, and tumor mutation load (TMB) data were downloaded from TCGA and GEO databases. The differentially expressed FAM genes (FAM DEGs) between cancer and control samples were screened, and their correlation with TMB and survival was analyzed. A PPI network of FAM DEGs was constructed, and a downscaling clustering analysis was performed based on the expression of the FAM DEGs. Further immuno- infiltration and GO/KEGG enrichment analyses of the identified FAM clusters were performed to explore their heterogeneity in biological functions. The effects of FAM score and gastric cancer (STAD) on TMB, MSI, survival prognosis, and drug sensitivity were jointly analyzed, and finally, a single-gene analysis of the obtained core targets was performed.</p><p><strong>Results: </strong>Through differential analysis, 68 FAM DEGs were obtained, and they were highly associated with STAD tumor mutation load. In addition, a high FAM DEGs CNV rate was observed. The PPI network showed a complex mutual correlation between the FAM DEGs. Consensus clustering classified the patients into three clusters based on the FAM DEGs, and the clusters presented different survival rates. The GSVA and immune infiltration analysis revealed that metabolism, apoptosis, and immune infiltration-related pathways were variated. In addition, FAM genes, STAD prognostic risk genes, and PCA scores were closely associated with the survival status of STAD patients. FAM score was closely correlated with STAD TMB, MSI, and immunotherapy, and the TMB values in the low FAM score group were significantly higher than those in the high FAM score group. Finally, combining the above results, it was found that the core gene PTGS1 performed best in predicting STAD survival prognosis and TMB/MSI/immunotherapy.</p><p><strong>Conclusion: </strong>Fatty acid metabolism genes affect the development of gastric adenocarcinoma and can predict the survival prognosis, tumor mutational load characteristics, and drug therapy sensitivity of STAD patients, which can help explore more effective immunotherapy targets for GC.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"666-680"},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199779","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":"Current Strategies for Overcoming Smoking Addiction: A Major Cause of Oral Cancer.","authors":"Rajakumar Govindasamy, Baskar Venkidasamy, Muthu Thiruvengadam","doi":"10.2174/1574892818666230220120507","DOIUrl":"10.2174/1574892818666230220120507","url":null,"abstract":"","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"123-125"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10753016","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":"A Patent Review of Human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors as Anticancer Agents and their Other Therapeutic Applications (1999-2022).","authors":"Pinky Gehlot, Vivek K Vyas","doi":"10.2174/1574892818666230417094939","DOIUrl":"10.2174/1574892818666230417094939","url":null,"abstract":"<p><p>Highly proliferating cells, such as cancer cells, are in high demand of pyrimidine nucleotides for their proliferation, accomplished by <i>de novo</i> pyrimidine biosynthesis. The human dihydroorotate dehydrogenase (hDHODH) enzyme plays a vital role in the rate-limiting step of <i>de novo</i> pyrimidine biosynthesis. As a recognised therapeutic target, hDHODH plays a significant role in cancer and other illness. In the past two decades, small molecules as inhibitors hDHODH enzyme have drawn much attention as anticancer agents, and their role in rheumatoid arthritis (RA), and multiple sclerosis (MS). In this patent review, we have compiled patented hDHODH inhibitors published between 1999 and 2022 and discussed the development of hDHODH inhibitors as anticancer agents. Therapeutic potential of small molecules as hDHODH inhibitors for the treatment of various diseases, such as cancer, is very well recognised. Human DHODH inhibitors can rapidly cause intracellular uridine monophosphate (UMP) depletion to produce starvation of pyrimidine bases. Normal cells can better endure a brief period of starvation without the side effects of conventional cytotoxic medication and resume synthesis of nucleic acid and other cellular functions after inhibition of <i>de novo</i> pathway using an alternative salvage pathway. Highly proliferative cells such as cancer cells do not endure starvation because they are in high demand of nucleotides for cell differentiation, which is fulfilled by <i>de novo</i> pyrimidine biosynthesis. In addition, hDHODH inhibitors produce their desired activity at lower doses rather than a cytotoxic dose of other anticancer agents. Thus, inhibition of <i>de novo</i> pyrimidine biosynthesis will create new prospects for the development of novel targeted anticancer agents, which ongoing preclinical and clinical experiments define. Our work brings together a comprehensive patent review of the role of hDHODH in cancer, as well as various patents related to the hDHODH inhibitors and their anticancer and other therapeutic potential. This compiled work on patented DHODH inhibitors will guide researchers in pursuing the most promising drug discovery strategies against the hDHODH enzyme as anticancer agents.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"280-297"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9373679","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":"KRAS Pathways: A Potential Gateway for Cancer Therapeutics and Diagnostics.","authors":"Pankaj Kumar Tripathi, Khushi R Mittal, Nandini Jain, Naveen Sharma, Chakresh Kumar Jain","doi":"10.2174/1574892818666230406085120","DOIUrl":"10.2174/1574892818666230406085120","url":null,"abstract":"<p><p>One of the major disturbing pathways within cancer is \"The Kirsten rat sarcoma viral oncogene homolog (KRAS) pathway\", and it has recently been demonstrated to be the most crucial in therapies and diagnostics. KRAS pathway includes numerous genes. This multi-component signaling system promotes cell growth, division, survival, and death by transferring signals from outside the cell to its interior. KRAS regulates the activation of a variety of signaling molecules. The KRAS oncogene is a key player in advancing a wide range of malignancies, and the mutation rank of this gene is a key feature of several tumors. For some malignancies, the mutation type of the gene may offer information about prognostic, clinical, and predictive. KRAS belongs to the RAS oncogene family, which consists of a compilation of minor GTP-binding proteins that assimilate environmental inputs and trigger internal signaling pathways that control survival, cell differentiation, and proliferation. This review aims to examine the recent and fascinating breakthroughs in the identification of new therapies that target KRAS, including the ever-expanding experimental approaches for reducing KRAS activity and signaling as well as direct targeting of KRAS. A literature survey was performed. All the relevant articles and patents related to the KRAS pathway, the mutation in the KRAS gene, cancer treatment, and diagnostics were found on PubMed and Google Patents. One of the most prevalent causes of cancer in humans is a mutation in the K-RAS protein. It is extremely difficult to decipher KRAS-mediated signaling. It allows transducing signals to go from the cell's outer surface to its nucleus, having an influence on a variety of crucial cellular functions including cell chemotaxis, division, dissemination, and cell death. Other involved signaling pathways are RAF, and the phosphatidylinositol 3 kinase also known as AKT. The EGFR pathway is incomplete without KRAS. The activation of PI3K significantly contributes to acquiring resistance to a mixture of MEK inhibitors and anti-EGFR in colorectal cancer cell lines which are mutated by KRAS. A series of recent patent studies towards cancer diagnostics and therapeutics reveals the paramount importance of mutated protein KRAS as an extensive driver in human tumors. For the prognosis, diagnosis, and treatment of colorectal cancer, KRAS plays a critical role. This review concludes the latest and vowing developments in the discovery of novel techniques for diagnosis and drugs that target KRAS, the advancements in experimental techniques for signaling and inhibiting KRAS function, and the direct targeting of KRAS for cancer therapeutics.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"268-279"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9267229","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":"Strategies for Developing Cancer Theranostics Approaches.","authors":"Zikang Wang, Wanhe Wang, Chung-Hang Leung","doi":"10.2174/1574892818666230510124139","DOIUrl":"10.2174/1574892818666230510124139","url":null,"abstract":"","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"130-136"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9498292","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":"1,3,4-Oxadiazoles as Anticancer Agents: A Review.","authors":"Greesh Kumar, Rajnish Kumar, Avijit Mazumder, Salahuddin, Upendra Kumar","doi":"10.2174/1574892818666230727102928","DOIUrl":"10.2174/1574892818666230727102928","url":null,"abstract":"<p><p>Among the deadliest diseases, cancer is characterized by tumors or an increased number of a specific type of cell because of uncontrolled divisions during mitosis. Researchers in the current era concentrated on the development of highly selective anticancer medications due to the substantial toxicities of conventional cytotoxic drugs. Several marketed drug molecules have provided resistance against cancer through interaction with certain targets/growth factors/enzymes, such as Telomerase, Histone Deacetylase (HDAC), Methionine Aminopeptidase (MetAP II), Thymidylate Synthase (TS), Glycogen Synthase Kinase-3 (GSK), Epidermal Growth Factor (EGF), Vascular Endothelial Growth Factor (VEGF), Focal Adhesion Kinase (FAK), STAT3, Thymidine phosphorylase, and Alkaline phosphatase. The molecular structure of these drug molecules contains various heterocyclic moieties that act as pharmacophores. Recently, 1,3,4- oxadiazole (five-membered heterocyclic moiety) and its derivatives attracted researchers as these have been reported with a wide range of pharmacological activities, including anti-cancer. 1,3,4- oxadiazoles have exhibited anti-cancer potential via acting on any of the above targets. The presented study highlights the synthesis of anti-cancer 1,3,4-oxadiazoles, their mechanism of interactions with targets, along with structure-activity relationship concerning anti-cancer potential.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"257-267"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9879267","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}
Yiping Zhou, Di Yang, Zihao Qiang, Yanfa Meng, Ruigang Li, Xiang Fan, Wei Zhao, Yao Meng
{"title":"Ribosome-inactivating Protein MAP30 Isolated from <i>Momordica Charantia L.</i> Induces Apoptosis in Hepatocellular Carcinoma Cells.","authors":"Yiping Zhou, Di Yang, Zihao Qiang, Yanfa Meng, Ruigang Li, Xiang Fan, Wei Zhao, Yao Meng","doi":"10.2174/1574892818666221103114649","DOIUrl":"10.2174/1574892818666221103114649","url":null,"abstract":"<p><strong>Background: </strong>Ribosome-inactivating proteins (RIPs) have been reported to exert antitumor and anti-virus activities. A recent patent CN202011568116.7 has developed a new method to prepare Momordica anti-HIV protein of 30 kDa (MAP30). MAP30 is a type I RIP, which kills various tumor cells through the N-glycosidase activity and irreversibly inhibits protein synthesis.</p><p><strong>Objective: </strong>To assess the potential role of MAP30 in inducing apoptosis of human hepatocellular carcinoma HCC-LM3 cells and elucidate the molecular mechanism of MAP30.</p><p><strong>Methods: </strong>CCK-8 assay was used to assess the proliferation of HCC-LM3 cells. Flow cytometry was used to measure the cycle, the level of ROS and apoptosis in HCC-LM3 cells. Western blots was used to measure protein levels.</p><p><strong>Results: </strong>Treatment with MAP30 reduced survival and proliferation of human liver cancer HCCLM3 cells in a dose-dependent manner. PI staining showed cell cycle arrest in G0/G1 phase. Furthermore, MAP30 increased the level of ROS in HCC-LM3 cells in 24 h treatment. To further confirm the role of MAP30 in inducing cell apoptosis, immunoblotting was carried out to detect the change of apoptosis-related proteins including PARP poly (ADP-ribose) polymerase (PARP- 1), Casepase3 and Cleaved-Caspase9. We found that PARP-1 and Caspase-3 were downregulated, whereas Cleaved-Caspase9 was up-regulated in HCC-LM3 cells treated with MAP30.</p><p><strong>Conclusion: </strong>This study indicated that MAP30 has the potential to be a novel therapeutic agent for human hepatocellular carcinoma.</p>","PeriodicalId":20774,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"223-232"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40665429","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}