Anti-cancer agents in medicinal chemistry最新文献

{"title":"Targeting RSK2 in Cancer Therapy: A Review of Natural Products.","authors":"Tianhui Wu, Ziming Chen, Xin Liu, Xinyan Wu, Zhaobo Wang, Weiqiang Guo","doi":"10.2174/0118715206329546240830055233","DOIUrl":"https://doi.org/10.2174/0118715206329546240830055233","url":null,"abstract":"<p><p>P90 ribosomal S6 kinase 2 (RSK2) is an important member of the RSK family, functioning as a kinase enzyme that targets serine and threonine residues and contributes to regulating cell growth. RSK2 comprises two major functional domains: the N-terminal kinase domain (NTKD) and the C-terminal kinase domain (CTKD). RSK2 is situated at the lower end of the Mitogen-activated protein kinases (MAPK) signaling pathway and is phosphorylated by the direct regulation of Extracellular signal-regulating kinase (ERK). RSK2 has been found to play a pivotal role in regulating cell proliferation, apoptosis, metastasis, and invasion in various cancer cells, including breast cancer and melanoma. Consequently, RSK2 has emerged as a potential target for the development of anti-cancer drugs. Presently, several inhibitors are undergoing clinical trials, such as SL0101. Current inhibitors of RSK2 mainly bind to its NTK or CTK domains and inhibit their activity. Natural products serve as an important resource for drug development and screening and with the potential to identify RSK2 inhibitors. This article discusses how RSK2 influences tumor cell proliferation, prevents apoptosis, arrests the cell cycle process, and promotes cancer metastasis through its regulation of downstream pathways or interaction with other biological molecules. Additionally, the paper also covers recent research progress on RSK2 inhibitors and the mechanisms of action of natural RSK2 inhibitors on tumors. This review emphasizes the significance of RSK2 as a potential therapeutic target in cancer and offers a theoretical basis for the clinical application of RSK2 inhibitors.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152995","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":"Lapatinib: A Potential Therapeutic Agent for Colon Cancer Targeting Ferroptosis.","authors":"Yue Sun, Dan Wang, Chen Yuan, Xiujuan Lang, Songbo Fu","doi":"10.2174/0118715206327756240830062531","DOIUrl":"https://doi.org/10.2174/0118715206327756240830062531","url":null,"abstract":"<p><strong>Background: </strong>Colon cancer poses a significant threat to the lives of several patients, impacting their quality of life, thus necessitating its urgent treatment. Lapatinib, a new generation of targeted anti-tumor drugs for clinical application, has yet to be studied for its molecular mechanisms in treating colon cancer.</p><p><strong>Objectives: </strong>This study aimed to uncover the underlying molecular mechanisms through which lapatinib exerts its therapeutic effects in colon cancer treatment.</p><p><strong>Methods: </strong>We accessed pertinent data on patients with colon cancer from the Cancer Genome Atlas (TCGA) database and performed bioinformatics analysis to derive valuable insights. The cell counting kit-8 (CCK8) assay was employed to assess whether lapatinib has a potential inhibitory effect on the growth and proliferation of HT- 29 cells. Additionally, we employed western blot and real-time quantitative polymerase chain reaction methods to investigate whether lapatinib regulates the expression of the ferroptosis-associated protein GPX4 in HT-29 cells. Furthermore, we utilized specific assay kits to measure the levels of reactive oxygen species (ROS) and malondialdehyde in HT-29 cells treated with lapatinib, aiming to elucidate the precise pattern of cell damage induced by this compound.</p><p><strong>Results: </strong>GPX4 exhibited high expression levels in tissues from patients with colon cancer and was significantly associated with patient prognosis and diagnosis. Lapatinib inhibited the growth and proliferation of the colon cancer cell line HT-29. Additionally, lapatinib suppressed the expression of GPX4 in HT-29 cells, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) partially restored its expression. Lapatinib induced an increase in intracellular ROS levels and malondialdehyde content in HT-29 cells, with Fer-1 partially restoring these levels.</p><p><strong>Conclusion: </strong>Our findings demonstrated that lapatinib could effectively suppress the mRNA and protein expression of GPX4 in colon cancer cells, which elevates intracellular levels of ROS and malondialdehyde, ultimately inducing ferroptosis in these cells. This mechanism underscores the potential of lapatinib as a therapeutic strategy for targeting tumors.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139059","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":"Effects of Arborvitae (Thuja plicata) Essential Oil on Cervical Cancer Cells: Insights into Molecular Mechanisms.","authors":"Ruben Piña-Cruz, Andrea Molina-Pineda, Marco Aguila-Estrada, María Martha Villaseñor-García, Georgina Hernández-Flores, Luis Felipe Jave-Suarez, Adriana Aguilar-Lemarroy","doi":"10.2174/0118715206308864240823095507","DOIUrl":"https://doi.org/10.2174/0118715206308864240823095507","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to assess the effects of AEO in an in vitro model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression.</p><p><strong>Background: </strong>Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from Thuja Plicata, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted.</p><p><strong>Objective: </strong>The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines.</p><p><strong>Methods: </strong>The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis.</p><p><strong>Results: </strong>The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells.</p><p><strong>Conclusion: </strong>Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124549","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":"Molecular Activities and Mechanisms of Action of Substances and Molecules from Medicinal Plants from Sub-Saharan Africa on Prostate and Cervical Cancer Cells.","authors":"Liz Laetitia Coulibaly, Bagora Bayala, Jacques Simpore","doi":"10.2174/0118715206321859240827045546","DOIUrl":"https://doi.org/10.2174/0118715206321859240827045546","url":null,"abstract":"<p><strong>Background: </strong>Despite years of medical research, cancer remains a major public health problem worldwide, particularly in Africa. The cost, duration, and toxicity of currently available treatments are all drawbacks. Plant secondary metabolites are significant anticancer compounds. Already used in traditional health systems, plants are currently the subject of numerous studies to discover new anti-cancer drugs.</p><p><strong>Objective: </strong>This review assesses the literature on the cytotoxic effect of plant substances (extracts) and molecules on prostate and cervical cancer cell lines.</p><p><strong>Method: </strong>PubMed, Science Direct, and Google Scholar were used to find in vitro studies carried out between 2006 and 2023 related to the cytotoxicity of extracts, substances and/or molecules from plants harvested in sub-Saharan Africa against prostate and/or cervical cancer cell lines.</p><p><strong>Results: </strong>A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases. All the plants listed had a cytotoxic effect on prostate and/or cervical cancer cells. Some plant extracts or molecules showed significant activity with an IC50< 20 μg/ml. Burkina Faso and South Africa had the most plant extracts tested for prostate and cervical cancer, respectively.</p><p><strong>Conclusion: </strong>A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124591","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":"FN-1501 Inhibits Diffuse Large B-Cell Lymphoma Tumor Growth by Inducing Cell Cycle Arrest And Apoptosis.","authors":"Dan Zou, Bowen Hu, Sitong Feng, Rujia Si, Bei Zhong, Bo Shen, Yuxin Du, Jifeng Feng","doi":"10.2174/0118715206345788240902062910","DOIUrl":"https://doi.org/10.2174/0118715206345788240902062910","url":null,"abstract":"<p><strong>Background: </strong>Due to its high degree of aggressiveness, diffuse large B-cell lymphoma (DLBCL) presents a treatment challenge because 30% to 50% of patients experience resistance or relapse following standard chemotherapy. FN-1501 is an effective inhibitor of cyclin-dependent kinases and Fms-like receptor tyrosine kinase 3.</p><p><strong>Objective: </strong>This study aimed to examine the anti-tumor impact of FN-1501 on DLBCL and clarify its molecular mechanism.</p><p><strong>Methods: </strong>This study used the cell counting kit-8 assay to evaluate cell proliferation, along with western blotting and flow cytometry to analyze cell cycle progression and apoptosis influenced by FN-1501 in vitro. Afterward, the effectiveness of FN-1501 was evaluated in vivo utilizing the xenograft tumor model. In addition, we identified the potential signaling pathways and performed rescue studies using western blotting and flow cytometry.</p><p><strong>Results: </strong>We found that FN-1501 inhibited cell proliferation and induced cell cycle arrest and apoptosis in DLBCL cells in vitro. Its anti-proliferative effects were shown to be time- and dose-dependent. The effect on cell cycle progression resulted in G1/S phase arrest, and the apoptosis induction was found to be caspase-dependent. FN-1501 treatment also reduced tumor volumes and weights and was associated with a prolonged progressionfree survival in vivo. Mechanistically, the MAPK and PI3K/AKT/mTOR pathways were significantly inhibited by FN-1501. Additional pathway inhibitors examination reinforced that FN-1501 may regulate cell cycle arrest and apoptosis through these pathways.</p><p><strong>Conclusion: </strong>FN-1501 shows promising anti-tumor activity against DLBCL in vivo and in vitro, suggesting its potential as a new therapeutic option for patients with refractory or relapsed DLBCL.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124589","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":"Immunomodulatory Roles of IL-15 in Immune Cells and its Potential for Cancer Immunotherapy.","authors":"Youhan Liu, Wen Ma, Xuewen Tian, Qinglu Wang, Xin Lu, Ying Luo, Jun Xv","doi":"10.2174/0118715206321574240821112747","DOIUrl":"https://doi.org/10.2174/0118715206321574240821112747","url":null,"abstract":"<p><p>Interleukin-15 (IL-15) was identified in 1994 as a T-cell growth factor with the capability to mimic the functions of IL-2. IL-15 engages with the IL-15Rα subunit expressed on the surface of antigen-presenting cells (APCs) and, through a trans-presentation mechanism, activates the IL-2/IL-15Rβγ complex receptor on the surface of natural killer (NK) cells and CD8+ T cells. This interaction initiates a cascade of downstream signaling pathways, playing a pivotal role in the activation, proliferation, and anti-apoptotic processes in NK cells, CD8+ T cells, and B cells. It provides a substantial theoretical foundation and potential therapeutic targets for tumor immunotherapy. Whether through active or passive immunotherapeutic strategies, IL-15 has emerged as a critical molecule for stimulating anti-tumor cell proliferation.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124590","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":"Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling, and Suppressing β-catenin-dependent Transcription.","authors":"Sara Sigler, Mohammad Abdel-Halim, Reem K Fathalla, Luciana Madeira Da Silva, Adam B Keeton, Yulia Y Maxuitenko, Kristy Berry, Gang Zhou, Matthias Engel, Ashraf H Abadi, Gary A Piazza","doi":"10.2174/0118715206318802240821114353","DOIUrl":"https://doi.org/10.2174/0118715206318802240821114353","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported that the cGMP-specific PDE5 isozyme is overexpressed in colon adenomas and adenocarcinomas and essential for colon cancer cell proliferation, while PDE5 selective inhibitors (e.g., sildenafil) have been reported to have cancer chemopreventive activity.</p><p><strong>Aim: </strong>This study aimed to determine the anticancer activity of a novel PDE5 inhibitor, RF26, using colorectal cancer (CRC) cells and the role of PDE5 in CRC tumor growth in vivo.</p><p><strong>Objective: </strong>The objective of this study was to characterize the anticancer activity of a novel celecoxib derivative, RF26, in CRC cells previously reported to lack COX-2 inhibition but have potent PDE5 inhibitory activity.</p><p><strong>Methods: </strong>Anticancer activity of RF26 was studied using human CRC cell lines. Its effects on intracellular cGMP levels, cGMP-dependent protein kinase (PKG) activity, β-catenin levels, TCF/LEF transcriptional activity, cell cycle distribution, and apoptosis were measured. CRISPR/cas9 PDE5 knockout techniques were used to determine if PDE5 mediates the anticancer activity of RF26 and validate PDE5 as a cancer target.</p><p><strong>Results: </strong>RF26 was appreciably more potent than celecoxib and sildenafil to suppress CRC cell growth and was effective at concentrations that increased intracellular cGMP levels and activated PKG signaling. RF26 suppressed β-catenin levels and TCF/LEF transcriptional activity and induced G1 cell cycle arrest and apoptosis within the same concentration range. CRISPR/cas9 PDE5 knockout CRC cells displayed reduced sensitivity to RF26, proliferated slower than parental cells, and failed to establish tumors in mice.</p><p><strong>Conclusion: </strong>Further evaluation of RF26 for the prevention or treatment of cancer and studying the role of PDE5 in tumorigenesis are warranted.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118831","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":"An In-depth Review on <i>Argemone mexicana</i> in the Management of Liver Health and Liver Cancer.","authors":"Istuti Saraswat, Anjana Goel, Jyoti Gupta","doi":"10.2174/0118715206307964240821051756","DOIUrl":"https://doi.org/10.2174/0118715206307964240821051756","url":null,"abstract":"<p><strong>Introduction: </strong><i>Argemone mexicana</i>, commonly known as the Mexican prickly poppy, has been historically employed in traditional medicine for various ailments, including liver disorders. Given the rising prevalence of liver diseases, including cancer, investigating the potential efficacy of <i>Argemone mexicana</i> in promoting liver health is of paramount importance. This review aims to provide a comprehensive analysis of the existing literature on the hepatoprotective and anticancer properties of <i>Argemone mexicana</i>.</p><p><strong>Methodology: </strong>A systematic literature search was conducted across PubMed, Google Scholar, and relevant botanical and pharmacological databases. Studies from various sources, including in vitro experiments, animal models, and clinical trials, were included in the review. The search focused on articles published up to 2010-2023, encompassing research that explored the botanical characteristics, chemical composition, traditional uses, and pharmacological properties of <i>Argemone mexicana</i>, specifically emphasizing its impact on liver health and cancer.</p><p><strong>Results: </strong>The review revealed a wealth of studies highlighting the diverse pharmacological properties of Argemone mexicana. The botanical composition includes compounds with antioxidant and anti-inflammatory potential, suggesting hepatoprotective effects. Studies using in vitro and in vivo models demonstrated promising outcomes regarding liver function improvement and inhibition of liver cancer cell proliferation. While some clinical studies supported the traditional uses of <i>Argemone mexicana</i>, further well-designed trials are warranted to establish its clinical efficacy.</p><p><strong>Conclusion: </strong>In conclusion, <i>Argemone mexicana</i> shows promise as a natural agent for promoting liver health and combating liver cancer. Bioactive compounds with antioxidant and anti-inflammatory properties suggest potential hepatoprotective effects. However, translating these findings into clinical practice requires further rigorous investigation, including well-designed clinical trials. This review provides a foundation for future research efforts aimed at elucidating the full therapeutic potential of <i>Argemone mexicana</i> in liver health and cancer management.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118830","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":"Evaluation of Novel Diaza Cage Compounds as MRP Modulators in Cancer Cells.","authors":"Henry Döring, David Kreutzer, Jannis von Veh, Christoph R Ritter, Andreas Hilgeroth","doi":"10.2174/0118715206331206240828111126","DOIUrl":"https://doi.org/10.2174/0118715206331206240828111126","url":null,"abstract":"<p><strong>Aim: </strong>Novel MRP modulators are needed to combat MRP-mediated multidrug resistance (MDR) in cancer cells.</p><p><strong>Background: </strong>Anticancer drug resistance is the main problem in cancer therapy. Causative multidrug efflux pumps are attractive target structures for the development of inhibitors of their activity.</p><p><strong>Objective: </strong>We synthesized novel cage dimeric 1,4-dihydropyridines to evaluate them as MRP modulators in cancer cells targeting MRP1, MRP2, and MRP4.</p><p><strong>Method: </strong>Cage compounds were synthesized by solution dimerization of monomeric 1,4-dihydropyridines and a final functionalization reaction. The MRP modulation was determined in cellular efflux assays by the use of the flow cytometry technique as well as cellular fluorescent measurements with each fluorescent substrate of the efflux pumps.</p><p><strong>Results: </strong>Difluoro phenyl and methoxy or dimethoxy benzyl substitutions were most favourable for the MRP1 and MRP2 inhibition, whereas monofluor phenyl and dimethoxy benzyl substitutions were most favourable for the MRP4 inhibition.</p><p><strong>Conclusion: </strong>Effective inhibitors were identified that were demonstrated to restore the respective cancer cell line sensitivity for the anticancer drug as a proof-of-concept that encourages further preclinical studies.</p>.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103695","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":"Pseudolaric Acid B Inhibits FLT4-induced Proliferation and Migration in Non-small Cell Lung Cancer.","authors":"Panpan Lei, Jinna Liang, Xinyue Su, Jiapan Gao, Bingxi Ren, Xiaoyu Ma, Yuxiu Zhang, Weina Ma","doi":"10.2174/0118715206313028240819103933","DOIUrl":"https://doi.org/10.2174/0118715206313028240819103933","url":null,"abstract":"<p><strong>Objectives: </strong>Non-Small Cell Lung Cancer (NSCLC) has attracted much attention on account of the high incidence and mortality of cancers. Vascular Endothelial Growth Factor Receptor 3 (VEGFR3/FLT4), which is a highly expressed receptor in NSCLC, greatly regulates cancer proliferation and migration. Pseudolaric Acid B (PAB) is a diterpenoid acid with antitumor activity isolated from Pseudolarix kaempferi. This study aimed to explore the inhibitory effect of PAB targeting FLT4 in NSCLC.</p><p><strong>Methods: </strong>Cell membrane chromatography was used to evaluate the affinity of PAB binding on FLT4. NCIH1299 cells were used in this study, and an MTT assay was performed to determine the anti-proliferation effect of PAB. Cell cycle analysis was conducted to study the cycle arrest of PAB. Wound healing and Transwell assays assessed the rate of cell migration. Western blot analysis evaluated the expression of related proteins.</p><p><strong>Results: </strong>PAB showed strong affinity to FLT4 with a KD value of 3.01 × 10- 6 M. Targeting FLT4 by PAB inactivated downstream P38MAPK and PI3K/AKT pathways, which inhibited the proliferation of NCI-H1299 cells. Meanwhile, PAB promoted G2/M phase arrest by influencing CyclinB1 and CDK1 complex formation to inhibit NCI-H1299 cell growth, but the effect was attenuated by knocking down the FLT4. Besides, PAB regulated MMP9 secretion through the Wnt/β-catenin signaling pathway to inhibit NCI-H1299 cell migration. However, the ability of PAB to inhibit migration was significantly weakened by FLT4 knockdown in NCI-H1299 cells.</p><p><strong>Conclusion: </strong>PAB can inhibit the proliferation and migration of NSCLC cells through targeting FLT4 and is expected to be a promising FLT4 inhibitor for NSCLC treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078871","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}