Anti-cancer agents in medicinal chemistry最新文献

{"title":"Unraveling the Resistance: Challenges and Advances in PARP Inhibitor Therapy for BRCA1/2 Breast Cancer.","authors":"Hongjun Tang, Jingsheng Chen, Kangwei Jiang, Jiangtao He, Fangming Tang, Dongbing Li, Yuye Wu","doi":"10.2174/0118715206381898250428064533","DOIUrl":"https://doi.org/10.2174/0118715206381898250428064533","url":null,"abstract":"<p><p>Breast cancer is the most prevalent malignant tumor among women globally, with breast cancer susceptibility genes (BRCA1 and BRCA2, BRCA1/2) mutations significantly increasing the risk of developing aggressive forms of the disease. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have shown promise in treating BRCA1/2-mutated breast cancer by exploiting deficiencies in homologous recombination (HR) repair. However, the emergence of acquired resistance poses a significant challenge. Our study examines the mechanisms of PARPi resistance in BRCA1/2-mutated breast cancer, synthesizing recent clinical advancements and identifying key resistance pathways, including HR recovery, DNA replication fork stability, and epigenetic modifications. We also highlight potential strategies to overcome these challenges to PARPi resistance, such as combination therapies and novel targets. Our comprehensive analysis aims to inform future clinical practices and guide the development of more effective treatment strategies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958977","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":"Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral Therapy Across Multiple Cancer Types.","authors":"Run-Bin Tan, Yeannie Hui-Yeng Yap","doi":"10.2174/0118715206379105250429115604","DOIUrl":"https://doi.org/10.2174/0118715206379105250429115604","url":null,"abstract":"<p><p>Talimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1) with deletions in ICP34.5 and ICP47 genes and GM-CSF insertion, T-VEC selectively replicates within the tumor cells, inducing lysis and releasing tumor-derived antigens while stimulating systemic antitumor immunity through dendritic cell activation. Although extensively studied for melanoma, its potential extends beyond this malignancy, with emerging applications in breast cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), and other solid tumors. This review synthesizes T-VEC's mechanism of action, leveraging dysregulated Ras signalling, impaired interferon pathways in cancer cells, its clinical outcomes, and safety profile across these indications. While prior literature emphasizes melanoma monotherapy and combinations with immune checkpoint inhibitors, less attention has been given to its efficacy in non-melanoma cancers and synergistic potential with chemotherapy or radiation therapy. By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges-systemic delivery, immune clearance, and biomarker development for patient selection-are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC's expanding role in cancer treatment, offering clinicians' and researchers' insights to optimize its therapeutic horizons across diverse malignancies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956579","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":"Baicalin Inhibits Lung Cancer Cell Proliferation and Migration via ALOX12-Mediated Ferroptosis.","authors":"Yishun Jin, JinYu Wen, Zhenbo Geng, Ling Wang, Wenzheng Fang, Hanqing Zhao, Xiaohua Yan, Biyin Chen, Hangju Hua, Wujin Chen, Jiumao Lin","doi":"10.2174/0118715206342238250428115441","DOIUrl":"https://doi.org/10.2174/0118715206342238250428115441","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains a leading cause of cancer-related mortality worldwide, primarily due to late-stage diagnosis and resistance to conventional therapies. Recent studies have highlighted the potential of natural compounds in enhancing the efficacy and reducing the side effects of conventional cancer treatments. Baicalin, a bioactive compound from Scutellaria baicalensis, exhibits significant anticancer properties.</p><p><strong>Objectives: </strong>This study aimed to investigate the role of baicalin in modulating lung cancer cell behavior through the arachidonate 12-lipoxygenase (ALOX12)-mediated ferroptosis pathway.</p><p><strong>Methods: </strong>We employed cyber pharmacology and molecular docking techniques to predict and validate the interaction between baicalin and ALOX12. In vitro experiments were conducted on A549 lung cancer cells to assess the effects of baicalin on cell proliferation, migration, and invasion. The expression levels of ALOX12, reactive oxygen species (ROS), and ferroptosis markers, such as Glutathione Peroxidase 4 (GPX4) and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), were measured.</p><p><strong>Results: </strong>Baicalin treatment significantly upregulated ALOX12 expression in lung cancer cells, and this upregulation was associated with a reduction in cell proliferation, migration, and invasion. Furthermore, baicalin-induced ferroptosis was characterized by increased ROS levels, iron accumulation, and elevated expression of GPX4 and ACSL4. These findings suggest that baicalin enhances ferroptosis through ALOX12 activation, synergistically inhibiting cancer cell growth.</p><p><strong>Conclusion: </strong>Baicalin significantly upregulated ALOX12 expression, promoted ferroptosis, and inhibited the proliferation and migration of A549 lung cancer cells. This finding provides evidence for the potential use of baicalin as a therapeutic agent for lung cancer and highlights the importance of ALOX12 in lung cancer treatment strategies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969772","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 Dihydropyrimidinones Synthesized through Modified Biginelli Reaction as Eg5 Kinesin Inhibitors with Potential Anti-cancer Effects: In vitro and In vivo Studies.","authors":"Mojgan Nejabat, Samin Ghorbani Moghadam, Vahid Eskandarpour, Masoud Nejabat, Mahda Sadat Nasrollahzadeh, Farzin Hadizadeh","doi":"10.2174/0118715206373183250324063523","DOIUrl":"https://doi.org/10.2174/0118715206373183250324063523","url":null,"abstract":"<p><strong>Background: </strong>Monastrol is a known kinesin Eg5 inhibitor. It is a dihydropyrimidine with 4-(mhydroxyphenyl) substituent. In contrast to taxols and vinca alkaloids, which, through targeting microtubules, affect both normal and cancer cells, kinesin inhibitors selectively target cancer cells.</p><p><strong>Objectives: </strong>In this study, m-hydroxyphenyl in monastrol was replaced with imidazolyl substituent, which has better water solubility and is found in the structure of many drugs and biologically active compounds. The effects of synthesized compounds were also investigated.</p><p><strong>Methods: </strong>Three series of monastrol-related dihydropyrimidinone derivatives were synthesized through a modified Biginelli reaction. The newly synthesized compounds were characterized by elemental analysis, LCMS, and NMR. Then, the structure-activity relationship (SAR) of synthesized compounds was evaluated by their toxicity, molecular docking scores, and results of molecular dynamic simulation. The compounds with more potential (4i, 4m, 5a, and 6a) were further investigated in vitro and in vivo for their anti-cancer effects.</p><p><strong>Results: </strong>The synthesized compounds could effectively reduce the ATPase activity of kinesins, which was consistent with the observation of G2/M arrest of cells in flow cytometry and confocal microscopy results. In addition, an increase in cells in the sub-G1 phase, along with the enhancement of the Bax/Bcl-2 ratio and overexpression of caspases 3, 9, and 8, suggested the apoptosis-inducing effects of compounds. Moreover, compounds showed potent anti-angiogenic effects via altering the expression of genes involved in angiogenesis, which was consistent with the reduced length of capillaries in the CAM test. The synthesized compounds could also demonstrate satisfactory in vivo results in the mice tumor model, which was in accordance with the findings of in vitro experiments.</p><p><strong>Conclusion: </strong>Novel dihydropyrimidinone derivatives synthesized via modified Biginelli reaction present promising potential as anti-cancer agents.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957047","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":"Enhanced Apoptosis in Pancreatic Cancer Cells through Thymoquinone-rich Nigella sativa L. Methanol Extract: Targeting NRF2/HO-1 and TNF-α Pathways.","authors":"Sümeyra Çetinkaya, İlknur Çınar Ayan, Hatice Gül Dursun, İpek Süntar, Kevser Taban, Hasya Nazlı Gök, Mithat Atak","doi":"10.2174/0118715206370057250421061226","DOIUrl":"https://doi.org/10.2174/0118715206370057250421061226","url":null,"abstract":"<p><strong>Aims: </strong>This study explores the therapeutic potential of Nigella sativa L. and its key bioactive compound, thymoquinone (TQ).</p><p><strong>Background: </strong>Pancreatic cancer presents a significant health challenge due to its aggressiveness and limited treatment options. N. sativa and its component TQ have demonstrated anticancer properties in other cancers, warranting exploration in pancreatic cancer models.</p><p><strong>Objective: </strong>To assess the antiproliferative, apoptotic, and anti-invasive effects of N. sativa extracts and TQ on pancreatic cancer cells, with a focus on modulating the NRF2/HO-1 and TNF-α signaling pathways.</p><p><strong>Method: </strong>MIA PaCa-2 and PANC-1 pancreatic cancer cell lines were treated with essential and fixed oils, methanol extracts (from Türkiye and Syria), and TQ. Cell viability, apoptosis, and invasiveness were assessed via XTT, Annexin V, and Matrigel assays, respectively. Gene expression and cytokine levels were evaluated using RTqPCR and ELISA. HPLC was conducted to confirm TQ concentrations in extracts.</p><p><strong>Result: </strong>The methanol extract of Türkiye-originated N. sativa seeds (TM) exhibited the highest cytotoxic effect, reducing cell viability in MIA PaCa-2 and PANC-1 at 0.05 mg/mL, while TQ significantly decreased viability at 20 μM. TM reduced MIA PaCa-2 and PANC-1 invasiveness (42±1.23 and 35±0.73, respectively) and contained a higher concentration of TQ (7.9168 ± 0.0561%) compared to the Syria-originated extract (SM).</p><p><strong>Conclusion: </strong>The findings suggest that TM and TQ exhibit strong anticancer potential by modulating key signaling pathways in pancreatic cancer cells, supporting their potential for further development as therapeutic agents in pancreatic cancer treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954230","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":"Synthesis and Biological Studies of Aurones Derivatives for its Anticancer Potential.","authors":"Kulkarni P Yogesh, Pramod L Ingale","doi":"10.2174/0118715206373750250414155841","DOIUrl":"https://doi.org/10.2174/0118715206373750250414155841","url":null,"abstract":"<p><strong>Background: </strong>Aurone based compounds exhibited antioxidant and anti-inflammatory potential and documented for their anticancer potential. The anticancer potential of aurone derivatives AU3, AU4, AU5, AU7, and AU10 is yet to be studied against breast cancer.</p><p><strong>Objective: </strong>The present work was undertaken to evaluate the anticancer potential of aurone based test compounds AU3, AU4, AU5, AU7, and AU10 in breast cancer cell lines MCF-7.</p><p><strong>Methods: </strong>The azaindole based aurones were synthesized by the condensing 4,6-dimethoxybenzofuran-3(2H)-one derivative with various indole aldehydes in the presence of sodium hydroxide. The MCF-7 breast cancer cell line was used to assess the cytotoxic effects of these compounds. Molecular docking studies of the synthesized compounds against the Cyclin-dependent kinase 2 (CDK2)/Cyclin A complex were conducted.</p><p><strong>Results: </strong>Our experimental findings demonstrated that AU3, AU4, AU5, AU7, and AU10 elicited significant effects on MCF-7 by virtue of its minimum cell viability, with IC50 values of 70.14 μM, 87.85 μM, 133.21 μM, 52.79 μM, and 99.55 μM, respectively, thus, exhibits potential anticancer action. Further, to corroborate the anticancer potential, we investigated mechanisms of action through molecular docking studies with the CDK2/Cyclin A complex (PDB: 6GUC) and their findings demonstrated that test compounds showed robust binding through various interactions, including hydrogen bonds, Pi-interactions, and Alkyl bonds with key residues such as Lys129, Asp127, Gln131, and Asp145. Test compounds AU3 and AU7, exhibited better binding affinities and diverse interaction profiles, suggesting a potent disruption of CDK2/Cyclin A activity.</p><p><strong>Conclusion: </strong>Thus, in conclusion, our findings revealed that AU3, AU4, AU5, AU7, and AU10 elicited anticancer action and their effects through CDK2/Cyclin A disruption.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958783","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":"Advancements in Metal Complexation of Pyridine Derivatives (2022-2024): A Pathway to Enhanced Anticancer Potency.","authors":"Nouf A Babteen","doi":"10.2174/0118715206378693250414044912","DOIUrl":"https://doi.org/10.2174/0118715206378693250414044912","url":null,"abstract":"<p><p>Cancer remains a major global health challenge, necessitating innovative therapies that selectively target cancer cells while sparing healthy tissues. Pyridine and its derivatives have gained prominence in medicinal chemistry for their structural diversity and biological activity. However, their therapeutic potential is often hindered by low bioavailability, poor solubility, and rapid metabolism. Metal complexation has emerged as a promising solution, with pyridine nitrogen serving as an excellent coordination site for transition metals. These pyridinemetal complexes enhance stability, bioavailability, and anticancer properties, exhibiting potent cytotoxicity through mechanisms like ROS generation, DNA intercalation, and apoptosis induction. This review highlights the latest progress (2022-2024) in the field, emphasizing the structural modifications, and mechanistic insights that have propelled pyridine-metal complexes as potent anticancer agents. Special attention is given to the role of metal complexation in enhancing the anticancer potency of pyridine derivatives, with examples of preclinical studies showing their efficacy against various cancer types. The findings emphasize the potential of pyridine-metal complexes as a transformative approach in oncology, bridging the gap between innovative chemical design and impactful therapeutic applications.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952845","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":"Identification of Flavonoid-based Hypoxia-inducible Factor-2 Alpha Inhibitors for the Treatment of Breast Cancer- In silico and In vitro Evidence.","authors":"Shahinaz, Mursaleen Baba, Ravi Gor, Chandrasudan Ramamurthy, Habeeb Shaik Mohideen, Satish Ramalingam, Thangavel Mahalingam Vijayakumar","doi":"10.2174/0118715206377378250414052656","DOIUrl":"https://doi.org/10.2174/0118715206377378250414052656","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BC) is a common malignancy that poses a serious threat to women's health. The hypoxic tumor microenvironment in BC promotes drug resistance, making hypoxia-targeted therapies crucial. Targeting hypoxia-inducible factors (HIFs), particularly HIF-2α, has emerged as a promising approach to inhibit tumor growth and improve response to chemotherapy and radiotherapy. However, further research is required to fully understand the role of HIF-2α to develop more effective treatments for BC.</p><p><strong>Aim: </strong>The aim of this study is to identify phytochemicals that target HIF-2α and evaluate their effects on the MCF-7 breast cancer cell line under hypoxic conditions.</p><p><strong>Methods: </strong>Molecular docking identified phytochemicals targeting HIF-2α, with high-affinity compounds undergoing stability evaluation via GROMACS molecular dynamics simulations. ADMET and toxicity assessments were performed using SwissADME and ProTox-3.0. In-vitro assays on hypoxic MCF-7 cells examined cell viability and gene expression. The expression of HIF-2α-regulated genes (VEGFA, CCND1, GLUT1) was analyzed by using qRT-PCR.</p><p><strong>Results: </strong>Molecular docking revealed that naringin (-8.2 Kcal/mol) and morin (-7.1 Kcal/mol) showed better binding affinity than the standard drug, belzutifan (-7.7 Kcal/mol). Dynamic simulations, including RMSD, RMSF, Hbond interactions, Rg, SASA, and PE, confirmed their strong binding potential. Morin, in particular, demonstrated more H-bond interactions and met Lipinski's Rule of Five, making it a promising candidate for in vitro studies. It reduced cell viability with an IC50 of 118 μM and significantly downregulated HIF-2α-associated genes.</p><p><strong>Conclusion: </strong>Morin demonstrated promising anti-cancer activity under hypoxic conditions by inhibiting HIF-2α in the hypoxia signaling pathway.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956514","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":"Methyl (Z)-2-(Isothioureidomethyl)-2-pentenoate Hydrobromide Induces Cell Cycle Arrest and Disrupts Mitosis in a Melanoma Cell Line.","authors":"Laura Sartori Assunção, Iara Patricia Kretzer, Jelver Alexander Sierra Restrepo, Leonidas João de Mello Junior, Flavio Augusto Rocha Barbosa, Misael Ferreira, Marcus Mandolesi Sá, Tânia Beatriz Creczynski-Pasa","doi":"10.2174/0118715206358941250413154017","DOIUrl":"https://doi.org/10.2174/0118715206358941250413154017","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Cancer is a global health burden. Despite advances in early detection and therapeutics, cancer prevalence continues to increase, underscoring the need for innovative therapeutic strategies. Dysregulation of cell death mechanisms is a hallmark of cancer that can lead to apoptosis evasion, which strongly contributes to tumor progression and therapy resistance. Isothiouronium salts have attracted attention as promising antitumor agents. This study aimed to evaluate the in vitro antitumor effect of an isothiouronium salt (ISMF08) on the B16F10 melanoma cell line.</p><p><strong>Methods: </strong>The antitumor properties of IS-MF08 were investigated by incubating B16F10 cells with the compound at different concentrations. Cytotoxicity was determined by the (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) (MTT) assay, cell cycle arrest and cell death mechanisms by flow cytometry, and morphological alterations by transmission electron microscopy. Physicochemical parameters related to druglikeness were predicted in silico using the SwissADME tool.</p><p><strong>Results: </strong>IS-MF08 was cytotoxic to melanoma cells, triggering cell cycle arrest and disrupting mitosis. The mechanism of cell death was compatible with apoptosis, as indicated by annexin V-FITC experiments and the relevant morphological changes in cell structure observed by transmission electron microscopy. SwissADME predicted that IS-MF08 has good physicochemical properties related to absorption and permeation.</p><p><strong>Conclusion: </strong>The numerous mechanisms of cell death triggered by IS-MF08 and its drug-likeness make it an interesting molecule in the search for new antitumor compounds, contributing to therapies targeting the dysregulation of cellular mechanisms such as apoptosis.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967524","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":"BCL6 Inhibitors Exhibit Therapeutic Effects on Breast Cancer Cells through the BCL6-STAT4 Pathway.","authors":"Zai Wang, Mengtian Tan, Junqi Zhang, Hang Ren, Xueshuai Ye","doi":"10.2174/0118715206364308250410104338","DOIUrl":"https://doi.org/10.2174/0118715206364308250410104338","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the roles of BCL6 and STAT4 in breast cancer, their biological functions, and their relationships with the prognosis of patients with breast cancer.</p><p><strong>Methods: </strong>Online databases were used to analyze the expression characteristics of BCL6 and STAT4 in breast cancer, as well as the correlation between STAT4 and both the prognosis of breast cancer patients and the biological function of breast cancer cells. BC cell lines, such as MCF7 and MDA-436 cells, were treated with the BCL6 inhibitor TP-021, and STAT4 and BCL6 mRNA expression levels were detected. Sh-RNAs were used to downregulate STAT4 in MCF7 and MDA-436 cells, and their proliferation ability was measured via a CCK-8 assay.</p><p><strong>Results: </strong>BCL6 expression was detected in BC cell lines and tissues, but the expression of STAT4 was downregulated in BC, and the expression level of STAT4 was negatively correlated with patient prognosis. Inhibition of BCL6 can increase the STAT4 level in BC cells and inhibit their proliferation ability in vitro. Poor prognosis may be related to the expression of STAT4 and the characteristics of immune cell infiltration in tumor tissues.</p><p><strong>Conclusion: </strong>BCL6 inhibitors demonstrated therapeutic effects on breast cancer cells through the BCL6-STAT4 pathway.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973251","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}