Anti-cancer agents in medicinal chemistry最新文献

{"title":"Quercetin and its Derivatives as Targeted Potential Anticancer Agents: Insight into Synthesis, Mechanism, and SAR Approaches.","authors":"Siddhant, Salahuddin, Avijit Mazumder, Svvnsm Lakshmi, Zabih Ullah, Siddharth, Rajnish Kumar, Mohamed Jawed Ahsan, Abdussalam, Abhijit Debnath","doi":"10.2174/0118715206488690261009031903","DOIUrl":"https://doi.org/10.2174/0118715206488690261009031903","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer remains a major global health challenge, with GLOBOCAN 2022 estimating around 20 million current cases and 9.7 million deaths, projected to surpass 35 million by 2050. This review aims to consolidate two decades of preclinical and translational evidence on quercetin, a naturally occurring pentahydroxyflavone widely distributed across fruits, vegetables, and other plant sources, as a multitargeted candidate for cancer prevention and therapy, with particular focus on its semisynthetic derivatization, mechanisms of action, and structure-activity relationships.</p><p><strong>Methods: </strong>This review compiles and critically examines preclinical studies investigating quercetin's chemical structure, pharmacological mechanisms, and therapeutic efficacy across a broad range of cancer types, with breast cancer receiving primary emphasis owing to the depth and mechanistic specificity of the available MCF- 7-centered literature, followed by substantial coverage of blood, lung, prostate, colon, and bladder cancers. The synthesis additionally incorporates SAR analysis of semisynthetic derivatives, relevant patent literature, computational studies, and available clinical evidence.</p><p><strong>Results: </strong>Quercetin exhibits significant anticancer potential through apoptosis induction, modulation of AMPK/mTOR signaling, and suppression of cancer stem cell (CSC) markers (CD44, CD133). Studies reveal its broad efficacy in breast, colon, and lung cancers, potent cytotoxicity against MCF-7 cells, and synergistic effects in combination with standard chemotherapeutics. Quercetin and its derivatives also counter multidrug resistance by modulating P-gp and BCRP transporters and enhance redox balance via redox-active analogs. Structure- activity relationship analysis identifies selective O-alkylation, methylation, and etherification, particularly at the 3- and 7-positions, as key strategies for enhancing potency and selectivity over native quercetin.</p><p><strong>Discussion: </strong>The multitargeted mechanisms of quercetin, combined with structure-guided semisynthetic optimization, position it as a promising candidate for precision oncology. Computational approaches including molecular docking and network pharmacology further support and extend these mechanistic findings, while emerging clinical studies provide early, if still preliminary, validation of quercetin's translational potential.</p><p><strong>Conclusion: </strong>Quercetin offers significant therapeutic promise as a naturally derived, semi synthetic tunable compound in precision oncology. Future research should prioritize formulation optimization, expanded clinical investigation, and integration of computational target-prediction tools to fully realize its anticancer potential.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223052","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":"Baicalein Exerts Cytotoxic Effects Through Cell Cycle Arrest and Mitochondria- Dependent Pathway in Ovarian Cancer Cells: In-Vitro and Computational Evaluation.","authors":"Juhi Rais, Asif Jafri, Shilpi Singh, Suaib Luqman, Puneet Khare, Juveriya Israr, Azfar Jamal, Mohammad Azhar Kamal, Zahraa Alali, Md Abul Barkat, Sahabjada Siddiqui, Md Arshad","doi":"10.2174/0118715206487623261005024023","DOIUrl":"https://doi.org/10.2174/0118715206487623261005024023","url":null,"abstract":"<p><strong>Introduction: </strong>Ovarian cancer remains one of the most prevalent and lethal gynecological malignancies globally, necessitating the exploration of novel therapeutic agents. Baicalein, a naturally occurring flavonoid, possesses potent antioxidant and anti-inflammatory properties and has recently gained attention for its anticancer potential. This study aimed to elucidate the anticancer efficacy and underlying molecular mechanisms of baicalein in human ovarian carcinoma PA-1 cells through comprehensive in vitro and in silico approaches.</p><p><strong>Methods: </strong>PA-1 cells were exposed to increasing concentrations of baicalein, and cytotoxicity was assessed using the MTT assay. Apoptotic induction was evaluated by measuring mitochondrial membrane potential (MMP), reactive oxygen species (ROS) induction, and nuclear morphological changes using DAPI, Hoechst/PI, and AO/EB staining. Cell cycle checkpoints were analyzed by flow cytometry. Apoptosis-related genes (p53, Bax, Puma, Noxa, and Bcl-2) expression was quantified using qRT-PCR. In silico molecular docking was performed using PyRx to predict interactions with key apoptotic proteins, while SwissADME was employed to assess pharmacokinetic properties and drug-likeness.</p><p><strong>Results: </strong>Baicalein significantly reduced PA-1 cell viability in a concentration-dependent manner and induced pronounced morphological changes characteristic of apoptosis. Treatment resulted in elevated ROS production, loss of MMP, nuclear condensation, and S-phase cell cycle arrest. Gene expression analysis demonstrated significant upregulation of pro-apoptotic markers (p53, Bax, Puma, and Noxa) alongside decreased expression of the anti-apoptotic gene Bcl-2. Molecular docking studies revealed favorable binding affinities of baicalein with apoptosis-regulating proteins, and SwissADME analysis confirmed acceptable drug-likeness and pharmacokinetic profiles.</p><p><strong>Discussion: </strong>These findings showed that baicalein induces apoptosis in ovarian cancer PA-1 cells via a ROSmediated, mitochondria-dependent pathway.</p><p><strong>Conclusion: </strong>This study highlights the potential of baicalein as a promising lead compound for the development of anticancer therapeutics.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219848","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":"Imatinib-Based Derivative: Synthesis, Computational Modeling, and Experimental Anticancer Activity.","authors":"Ravshan Saidov, Shokhid Gulyamov, Laziz Elmurodov, Mukhriddin Makhkamov, Jamoliddin Razzokov, Nagendra Kumar Kaushik, Andrea Bencini, Piaoping Yang, Avez Sharipov","doi":"10.2174/0118715206488881261009110240","DOIUrl":"https://doi.org/10.2174/0118715206488881261009110240","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Cancer remains one of the major causes of death worldwide. Tyrosine kinase inhibitors (TKIs) represent an important class of targeted anticancer agents because they block key oncogenic signaling pathways. Imatinib mesylate was among the first TKIs introduced in clinical oncology and has significantly improved the treatment of several malignancies. Nevertheless, its clinical use is associated with adverse effects, which highlights the need to develop modified derivatives with improved efficacy and reduced toxicity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the present work, a new compound, imatinib aescinate, was prepared by dissolving imatinib and aescin separately in ethyl alcohol and combining the solutions under continuous stirring, followed by filtration and acetone-induced precipitation. For identification and structural characterization, the compound was analyzed using UV and FTIR spectroscopy, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD), thermogravimetric-differential thermal analysis (TGA/DTA), and HPLC. Antiproliferative activity was assessed in MCF-7 breast cancer cells using a CCK-8 cell viability assay (24 h), and wound closure was evaluated using a scratch assay. To understand potential molecular interactions, molecular dynamics simulations together with MM-PBSA binding energy calculations were also performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The synthesized compound exhibited greater antiproliferative activity against MCF-7 cells than either imatinib mesylate or aescin alone. The IC50 values determined from a 24 h CCK-8 assay were: imatinib aescinate 15.16 μM, aescin alone 23.55 μM, and imatinib mesylate 76.66 μM. Imatinib aescinate also inhibited MCF-7 wound closure in a concentration-dependent manner in the scratch assay. Computational analysis indicated stable binding of imatinib aescinate to the BCR-ABL tyrosine kinase (PDB ID: 2HYY). Molecular dynamics simulations suggested reduced conformational flexibility of the protein-ligand complex, and MM-PBSA calculations supported favorable binding energy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Imatinib aescinate was approximately fivefold more potent than imatinib mesylate and 1.6-fold more potent than aescin, indicating enhanced antiproliferative activity. Its concentration-dependent inhibition of wound closure also suggests potential antimigratory effects, although reduced cell proliferation may contribute to this result. Computational findings supported stable and favorable binding to BCR-ABL; however, the underlying mechanism requires experimental confirmation. Further studies should evaluate kinase inhibition, toxicity, and in vivo efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, the results indicate that imatinib aescinate shows enhanced antiproliferative activity against MCF-7 cells compared with its individual components. Computational predictions suggest that the compound may interact with kina","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219832","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":"Magnetic and Non-Magnetic Halloysite Nanotubes Functionalized with Folic Acid for the Targeted Delivery of [Pd(dipic)Cl].H2O: Cytotoxicity and Apoptosis Induction in Colon Cancer Cells.","authors":"Run Wang, Mostafa Heidari Majd","doi":"10.2174/0118715206469146260925070750","DOIUrl":"https://doi.org/10.2174/0118715206469146260925070750","url":null,"abstract":"<p><strong>Introduction: </strong>Cisplatin and its analogs are commonly used in cancer therapy, but the lack of differentiation between healthy and cancer cells often leads to severe side effects.</p><p><strong>Methods: </strong>To address this problem, magnetic and non-magnetic Halloysite Nanotubes (HNTs) modified with folic acid (Fe-HNTs-FA and HNTs-FA) were developed, and the [Pd(dipic)Cl].H2O complex was encapsulated inside them. Cell viability was measured using the MTT assay. Real-time PCR was used to evaluate apoptosisrelated genes and the drug resistance marker. Oxidative stress in erythrocytes was assessed to confirm biocompatibility.</p><p><strong>Results: </strong>The Encapsulation Efficiency (EE%) of [Pd(dipic)Cl].H2O in the pores of Fe-HNTs-FA was found to be 29%. Fe-HNTs-FA-[Pd(dipic)Cl].H2O reduced cell viability to below 50%. HNTs-FA-[Pd(dipic)Cl].H2O showed cytotoxic effects at higher concentrations. The [Pd(dipic)Cl].H2O complex and cisplatin did not effectively inhibit the growth of HCT116 colon cancer cells. Real-time PCR analysis showed that the presence of Fe3O4 Nanoparticles (NPs) on Fe-HNTs-FA-[Pd(dipic)Cl].H2O increased the Bak1/Bclx ratio by 14.4-fold compared to the control group. Other compounds only increased the expression of caspase-3. The expression level of AKT1 was 1.39 for the free complex, and 0.076 and 0.078 for Fe-HNTs-FA-[Pd(dipic)Cl].H2O and HNTs-FA- [Pd(dipic)Cl].H2O, respectively. Furthermore, the modified HNTs did not induce oxidative stress in erythrocytes.</p><p><strong>Discussion: </strong>This targeted delivery induced apoptosis via extrinsic and intrinsic pathways, increased caspase-3 activation, and abolished drug resistance by downregulating AKT1 expression. The Fe-HNTs-FA- [Pd(dipic)Cl].H2O showed the potential to be a safer and more effective alternative to cisplatin without causing oxidative damage to erythrocytes.</p><p><strong>Conclusion: </strong>The positive properties of Fe-HNTs-FA-[Pd(dipic)Cl].H2O make it a promising candidate for targeted therapy of colon cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134612","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":"Exploratory Evaluation of Resveratrol-Thymoquinone Cytotoxic Interactions and Apoptotic Responses in MDA-MB-231 Triple-Negative Breast Cancer Cells.","authors":"Mustafa Nisari, Filiz Disçi, Yağmur Yaşar Fırat, Neriman İnanç","doi":"10.2174/0118715206499937260909092532","DOIUrl":"https://doi.org/10.2174/0118715206499937260909092532","url":null,"abstract":"<p><strong>Introduction: </strong>Diet-derived bioactive antioxidants have attracted increasing attention due to their potential role in modulating cancer-related pathways. This study aimed to investigate the cytotoxic and apoptotic effects of resveratrol and thymoquinone, individually and in combination, and to evaluate their potential synergistic interaction in aggressive MDA-MB-231 breast cancer cells.</p><p><strong>Methods: </strong>The cytotoxic effects of resveratrol and thymoquinone were evaluated in MDA-MB-231 cells using the MTT assay, and IC50 values were calculated. Combination doses were determined based on the cytotoxic concentrations obtained from single treatments. Drug interaction analysis was performed using the Chou- Talalay method to calculate combination indices (CI) from the MTT results. Each experiment was performed in three independent biological replicates. Apoptotic effects were assessed by Annexin V staining analysis.</p><p><strong>Results: </strong>Combination index values of resveratrol and thymoquinone were found to be <1, indicating a synergistic interaction between the two compounds. Annexin V staining analysis revealed that the proportion of late apoptotic cells was significantly higher in the combination treatment than in the individual treatments.</p><p><strong>Discussion: </strong>The present findings indicate that the combined administration of resveratrol and thymoquinone enhances cytotoxic effects in MDA-MB-231 cells through synergistic interactions at the tested concentration pairs. The higher proportion of late apoptotic cells observed with the combined treatment indicates that apoptosis contributes to the cellular response associated with reduced metabolic viability. However, the molecular pathways underlying this response were not directly investigated. Therefore, potential involvement of oxidative stress, mitochondrial dysfunction, and apoptosis-related signaling requires direct molecular validation. Because no non-malignant breast epithelial cell line was included, the cancer-cell selectivity of these effects could not be determined.</p><p><strong>Conclusion: </strong>The combination of resveratrol and thymoquinone was associated with a greater apoptotic response than the individual treatments and demonstrated synergistic cytotoxic interactions at the tested concentration pairs in MDA-MB-231 cells. These preliminary findings require confirmation in non-malignant breast epithelial cells, additional breast cancer models, and molecularly characterized experimental systems.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134494","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":"Drug Repositioning of Cardiac Steroids as Potential Agents for the Treatment of Triple‑Negative Breast Cancer.","authors":"Sara A Al-Shun, Magdy M Youssef, Farid A Badria","doi":"10.2174/0118715206446104260116044525","DOIUrl":"https://doi.org/10.2174/0118715206446104260116044525","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-Negative Breast Cancer (TNBC) lacks targeted therapies and is mainly treated with chemotherapeutics limited by toxicity and resistance. This study aims to identify and characterize cardiac steroids as potential anti-TNBC leads using phenotypic screening, drug-likeness evaluation, and in silico targetprofiling.</p><p><strong>Methods: </strong>A panel of natural products was screened against TNBC MDA-MB-231 cells using MTT assay and compared with conventional chemotherapeutics; selectivity indices were calculated using WI-38 fibroblasts. SwissADME was used to predict physiochemical and pharmacokinetic properties. Putative targets of the top hit were predicted, intersected with breast-cancer-associated genes, and subjected to Protein-Protein Interaction (PPI) and enrichment analyses to identify hub targets. VEGFA was selected for Molecular Docking and (MD) molecular dynamics simulations with digitoxigenin.</p><p><strong>Results: </strong>The cardiac steroids digitoxin, digitoxigenin, and ouabain exhibited the greatest potency with lownanomolar IC₂⁽ values that markedly surpassed those of cisplatin, doxorubicin, and sorafenib. Digitoxigenin displayed the most favorable selectivity (SI = 4.2). SwissADME favored digitoxigenin over digitoxin with no Lipinski violations. Target-profiling highlighted angiogenesis- and signaling-related hub proteins, including VEGFA. Molecular docking and MD simulations suggested a stable digitoxigenin-VEGFA complex.</p><p><strong>Discussion: </strong>These data support digitoxigenin as a prioritized cardiac steroid scaffold that combines potent in vitro cytotoxicity with improved selectivity and a more favorable drug-likeness profile than digitoxin, while the in silico analyses provide a mechanistic hypothesis centered on angiogenesis and survival signaling.</p><p><strong>Conclusion: </strong>Digitoxigenin emerges as a promising anti-TNBC lead. The in silico analyses generate mechanistic hypotheses that warrant future biochemical validation and in vivo efficacy and cardiotoxicity studies in TNBC models.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134882","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":"Enhancing Cancer Immunotherapy with Berberine and Its Loaded Nanoparticles: A Systematic Review.","authors":"Mohadeseh Karimian, Saber Abbaszadeh, Kosar Farhadi Babadi, Alizamen Salehifard Jouneghani, Saeid Heidari-Soureshjani, Catherine Mt Sherwin","doi":"10.2174/0118715206508700260918112844","DOIUrl":"https://doi.org/10.2174/0118715206508700260918112844","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Neoplasms are considered a health problem around the world. This study systematically examines the effects of Berberine (BBR) and BBR-loaded Nanoparticles (NPs), with an emphasis on elucidating the molecular and cellular mechanisms through which these formulations enhance cancer immunotherapy.</p><p><strong>Methods: </strong>A systematic literature search (on December 17, 2025) was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library electronic databases. Related articles aligned with our study aim were screened, and the required data were extracted and recorded in a table. Moreover, the risk of bias for both in vitro and in vivo publications was assessed.</p><p><strong>Results: </strong>Finally, 22 studies were included in the screening process. BBR and its NPs potentially improved immunotherapy outcomes by reducing Programmed Cell Death 1 Receptor (PD-L1) expression (relieving PD-1/PD-L1-mediated immunosuppression), cytokine modulation, immune cell activation and infiltration, repolarization of macrophages from M2 to M1 phenotype, increasing T-cell-mediated cytotoxicity, disrupting mitochondrial membrane potential, and promoting the accumulation of intracellular Reactive Oxygen Species (ROS), inducing pyroptosis and immunogenic cell apoptosis in various cancerous cell lines. BBR NPs reduced systemic toxicity, improved sustained drug release, solubility, and drug targeting in tumor cells.</p><p><strong>Discussion: </strong>BBR and nanoformulated BBR enhance immunotherapy and drug delivery. However, limitations of this review were a lack of standardized study design techniques and clinical trial studies. Future studies should focus on cell toxicity, dose-effectiveness, and clinical translation.</p><p><strong>Conclusion: </strong>BBR and its NPs showed favorable immunomodulatory properties and enhanced cancer immunotherapy in experimental studies. However, more clinical studies are needed in this field.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134866","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":"HnRNPA1-Regulated miR-23a-3p Promotes Hepatocellular Carcinoma Metastasis by Targeting the PTEN Signaling Pathway.","authors":"Weiwei Wang, Sen Lu, Feng Jiao, Dayong Zhou, Guoyong Han, Jinwei Qi, Xinli Huang","doi":"10.2174/0118715206433797260923093404","DOIUrl":"https://doi.org/10.2174/0118715206433797260923093404","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Hepatocellular carcinoma (HCC) accounts for 75-85% of primary liver cancer cases and remains a major cause of cancer-related mortality worldwide. Despite its high incidence, there is currently no definitive cure for most patients, and the underlying molecular mechanisms are not fully understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;HCC cells were used as an in vitro HCC model. Cells were divided into five groups: control, HnRNPA1 mimic, HnRNPA1 inhibitor, miR-23a-3p mimic, and miR-23a-3p inhibitor. HnRNPA1 and miR-23a-3p were overexpressed or silenced by transient transfection with specific mimics or inhibitors, respectively. Cell migration and apoptosis were assessed using Transwell assays and Annexin V/PI-based flow cytometry. The mRNA and protein expression levels of HnRNPA1, miR-23a-3p, PTEN, and related markers were measured by quantitative real-time PCR and Western blotting. Dual luciferase reporter assays were performed to validate the direct interaction between miR-23a-3p and the 3' untranslated region of PTEN and to examine the regulatory relationship between HnRNPA1 and miR-23a-3p.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Overexpression of HnRNPA1 increased its mRNA level by approximately 2.5-fold compared with the control group (P &lt; 0.01), enhanced Hep3B cell migration by about 60%, and reduced the apoptosis rate by roughly 50% (both P &lt; 0.01). These changes indicate that elevated HnRNPA1 expression markedly strengthens the migratory capacity of HCC cells and significantly suppresses their apoptosis, thereby conferring a clear pro-tumorigenic phenotype. Similarly, miR-23a-3p overexpression elevated its expression by about 3.3-fold (P &lt; 0.01), promoted cell migration by approximately 57%, and decreased apoptosis by around 43% relative to control (all P &lt; 0.01), further supporting the role of miR-23a-3p as a potent enhancer of HCC cell motility and survival. HnRNPA1 overexpression significantly up-regulated miR-23a-3p levels (≈2.1-fold, P &lt; 0.01), suggesting that HnRNPA1 positively regulates miR-23a-3p in HCC cells. Dual-luciferase reporter assays confirmed that miR-23a-3p directly binds to the 3'-untranslated region of PTEN, and miR-23a-3p overexpression markedly decreased PTEN mRNA and protein levels by approximately 42% and 34%, respectively (P &lt; 0.01). Functionally, restoring PTEN expression attenuated the miR-23a-3p-induced increase in cell migration by about 31% and partially reversed its anti-apoptotic effect (apoptosis increased by roughly 27% compared with the miR-23a-3p mimic group; P &lt; 0.05), indicating that suppression of PTEN is a critical downstream event by which the HnRNPA1/miR-23a-3p axis drives HCC progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The research results show that HnRNPA1, miR-23a-3p, and PTEN play crucial roles in the progression of liver cancer. These molecules interact within a regulatory network that may become a therapeutic target.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;HnRNPA1, miR-23a-","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103165","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":"Phenanthrene Derivatives from Arundina graminifolia Inhibit the Migration and Proliferation of Human Bladder Cancer Cells.","authors":"Xingyu Zhang, Songlin Yu, Shiquan Liu, Meifeng Liu","doi":"10.2174/0118715206468591260831073644","DOIUrl":"https://doi.org/10.2174/0118715206468591260831073644","url":null,"abstract":"<p><strong>Introduction: </strong>Arundina graminifolia (D. Don) Hochr. has been used in traditional Dai medicine for the treatment of urinary tract infections and related diseases for centuries.</p><p><strong>Methods: </strong>The cytotoxic effects of phenanthrene compounds on the human bladder cancer cell line 5637 were evaluated using the CCK-8 assay. The apoptosis-related effects of these compounds were further investigated. Changes in cell migration ability were assessed using the Transwell assay. In addition, the expression levels of proteins associated with these processes were examined by Western blot analysis.</p><p><strong>Results: </strong>Seven phenanthrene compounds isolated from A. graminifolia exhibited moderate to strong antiproliferative activities against 5637 bladder cancer cells, with IC50 values ranging from 38 to 87 μM. Among them, shancidin and densiflorol B showed more potent inhibitory effects on cell proliferation in a dose-dependent manner.</p><p><strong>Discussion: </strong>Shancidin and densiflorol B inhibited bladder cancer cell migration by modulating the expression of Epithelial-Mesenchymal Transition (EMT)-related proteins, including E-cadherin, vimentin, and ZO-1. In addition, these compounds may exert their anticancer effects by regulating key proteins involved in cell cycle progression and signaling pathways, including p27, ERK, and components of the PI3K/AKT and MAPK pathways. Overall, the tested phenanthrenes suppressed the proliferation and migration of bladder cancer cells by modulating EMT-related markers and associated signaling pathways.</p><p><strong>Conclusion: </strong>These findings suggest that phenanthrene derivatives from A. graminifolia may serve as promising lead compounds for the development of anti-bladder cancer agents.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036087","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":"Poly (Lactic-co-glycolic Acid)-Based Nanoparticles for Co-delivery and Targeted Delivery of Polyphenols in Cancer Therapy.","authors":"Reyhan Dilsu Colpan","doi":"10.2174/0118715206516168260917080151","DOIUrl":"https://doi.org/10.2174/0118715206516168260917080151","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer remains a leading cause of mortality worldwide, and current conventional therapies are often limited by systemic toxicity, drug resistance, and tumour recurrence. Although natural polyphenols, such as Curcumin (CUR), Quercetin (QUE), Caffeic Acid Phenethyl Ester (CAPE), Resveratrol (RSV), and Genistein (GEN), exhibit promising anticancer properties, their clinical translation is hindered by poor solubility, chemical instability, rapid metabolism, and low bioavailability. As biodegradable polymers have been approved by the Food and Drug Administration (FDA), Poly (lactic-co-glycolic acid) (PLGA)-based Nanoparticles (NPs) represent a promising delivery platform to overcome these limitations by enabling both passive and active tumour targeting.</p><p><strong>Methods: </strong>This review evaluates PLGA-based nanoparticle formulations for polyphenol delivery in cancer therapy, with an emphasis on single-drug delivery, co-encapsulation strategies (polyphenol-polyphenol and polyphenol-chemotherapeutic combinations), and functionalised targeted systems (e.g., folic acid-, transferrin-, ligand-, or peptide-mediated targeting). Studies conducted in two-dimensional (2D) and Three- Dimensional (3D) in vitro models, as well as in vivo models, are also discussed.</p><p><strong>Results: </strong>Overall, PLGA NPs significantly improved the therapeutic activity of polyphenols by enhancing their stability, pharmacokinetics, and tumour accumulation via passive and active targeting mechanisms. Co-encapsulation and targeted delivery strategies show enhanced growth inhibition activity compared to free polyphenols and non-functionalised PLGA NPs.</p><p><strong>Discussion: </strong>The activity of targeted PLGA co-delivery systems is attributed to the synergistic modulation of signalling pathways and improved intracellular accumulation via active targeting. This multifunctional delivery platform may serve as a strategy for combination cancer therapy by addressing the key pharmacokinetic limitations of polyphenols.</p><p><strong>Conclusion: </strong>Despite encouraging preclinical outcomes, several challenges remain, including batch-tobatch variability, large-scale production, long-term toxicity, immune responses, and clinical translation. Therefore, future studies should prioritise the development of stimuli-responsive, biomimetic, and personalised nanomedicine approaches to improve clinical applicability.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036079","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}