Anti-cancer agents in medicinal chemistry最新文献

{"title":"State of the Art of IDH Inhibitors: Emerging Questions and Perspectives.","authors":"João A L de Lima, Lídia Moreira Lima","doi":"10.2174/0118715206382095250908095950","DOIUrl":"https://doi.org/10.2174/0118715206382095250908095950","url":null,"abstract":"<p><p>Isocitrate Dehydrogenases (IDH) are ubiquitous enzymes essential for cellular metabolism, including the Krebs cycle, glutamine metabolism, lipogenesis, and redox balance. Mutations in IDH1 and IDH2 are implicated in several tumors - gliomas, Acute Myeloid Leukemia (AML), cholangiocarcinoma - altering enzyme activity and causing the overproduction of 2-hydroxyglutarate (2-HG). This oncometabolite disrupts α-KGdependent proteins, impairing key processes such as differentiation, division, and DNA repair. Understanding these genetic, biochemical, and clinical aspects has made IDH enzymes promising therapeutic targets, prompting the development of targeted inhibitors for tumors harboring IDH1 or IDH2 point mutations. Selective inhibitors like ivosidenib (AG-120) and enasidenib (AG-221), targeting mutant IDH1 and IDH2 respectively, block 2- HG production and induce differentiation, achieving clinical success - particularly in AML. However, resistance due to secondary mutations, especially in the allosteric binding site, remains a major obstacle. In response, novel approaches have emerged, such as covalent inhibitors like LY3410738, which irreversibly bind mutant residues, and dual inhibitors like vorasidenib (AG-881), which act on both IDH1 and IDH2 mutations and penetrate the blood-brain barrier for treating solid tumors. Still, many clinical factors must be considered. This review explores the current landscape of IDH-targeted therapies, emphasizing the need for novel inhibitors and highlighting innovative strategies, including the design of smaller, more potent molecules with favorable pharmacokinetics and the potential of drug repositioning. We underscore that discovering new antitumor compounds targeting IDH requires a collaborative effort across biomedical fields. These advancements aim to overcome resistance, broaden therapeutic options, and improve the effectiveness of IDH-targeted treatments.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079527","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":"Targeting WWPI HECT Domain by Small Inhibitors for Restoring PTEN Tumor Suppressive Role in Glioblastoma Therapy.","authors":"Atta Ullah, Majid Khan, Sadeeq Ur Rahman, Usama Qayum, Najeeb Ur Rehman, Magda H Abdellattif, Magdy Mohamed Ahmed Elshamy, Alaa Abu Alnjaa, Sobia Ahsan Halim, Ajmal Khan, Ahmed Al-Harrasi","doi":"10.2174/0118715206387854250811103423","DOIUrl":"https://doi.org/10.2174/0118715206387854250811103423","url":null,"abstract":"<p><strong>Introduction: </strong>PTEN (Phosphatase and tensin homolog) is a valuable regulator of the PI3K-AKT and mTOR pathways and is frequently mutated in cancer-like glioblastoma. The WWPI HECT domain has a group of enzymes called E3 ligases that ubiquitinate and inactivate PTEN by binding to it, which ultimately inhibits its lipid phosphatase function and promotes nuclear delocalization. This investigation seeks to restore the PTEN tumor suppressive activity by inhibiting the WWPI HECT domain in-silico.</p><p><strong>Methods: </strong>We virtually screened a library of ~960 compounds in the active pocket of the human WWPI HECT domain, and fifteen compounds were chosen based on their favorable binding affinities and highly negative docking scores.</p><p><strong>Results: </strong>Among those hits, five compounds, C5, C6, C8, C9 and C11, properly fit the standard with favorable pharmacokinetic and drug-like quality. Their capacity to suppress cell propagation was evaluated in the U87 glioma cell line. The compounds (C5, C6, C8, C9 and C11) exhibited significant anti-proliferative capability with IC50 values of 6.98 ± 0.14 μM, 14.58 ± 1.49 μM, 11.12 ± 0.73 μM, 13.85 ± 1.63 μM and 18 ± 1.23 μM, respectively.</p><p><strong>Discussion: </strong>Strong inhibitory action against glioma cells was shown by the discovered compounds, especially C5 and C8, suggesting that they may be able to restore PTEN tumor suppressive capabilities. A potential therapeutic intervention mechanism for glioblastoma is suggested by their interaction with the WWPI HECT domain.</p><p><strong>Conclusion: </strong>This study has discovered novel inhibitors against the WWPI HECT domain, and a treatment option for glioblastoma.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063311","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":"The Promising Role of PKM2 in the Diagnosis and Prognosis of Ovarian Cancer.","authors":"Praveen Kumar Borra, Phool Chandra, Himanshu Sharma, Sadaf Fatima, Anupama Koneru, Lavanya Athilli, Farsiya Fatima, Nagalla Bhargav Kumar, Neetu Sachan","doi":"10.2174/0118715206394408250806065235","DOIUrl":"https://doi.org/10.2174/0118715206394408250806065235","url":null,"abstract":"<p><p>PKM2 has emerged as a critical biomarker with the potential to enhance both diagnostic accuracy and therapeutic strategies in ovarian cancer. Due to its high fatality rate and difficulty identifying early signs, ovarian cancer remains a major global health concern. Biomarkers, particularly PKM2, provide targeted therapeutic methods and early detection. The complex role of PKM2 in cancer metabolism highlights its importance as a diagnostic biomarker, particularly through its involvement in the Warburg effect. Its interaction with key signaling pathways and tissue-specific expression patterns makes it a compelling target for personalized therapeutic strategies. Moreover, the detection of PKM2 in the blood of cancer patients further underscores its clinical utility and therapeutic relevance. Beyond diagnostics, PKM2 is also a promising therapeutic target. Preclinical research has reported that both activators and inhibitors of this protein are effective. For PKM2-based treatments to be successfully incorporated into clinical practice, extensive research and rigorous validation are required. To overcome the difficulties in managing ovarian cancer and accomplish the objective of improved early detection and individualised treatment methods, collaboration among the research, healthcare, and advocacy sectors is crucial. In conclusion, PKM2 represents a promising target in the fight against ovarian cancer, with the potential to improve diagnostic accuracy, therapeutic strategies, and overall patient survival.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013695","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":"Unveiling the Distinct Effects of a Two-Dimensional Copper/Sodium Complex: Oxidative Stress on Erythrocytes and Cytotoxicity, Apoptosis, Drug Resistance, and Inflammation in Lung Cancer Cells.","authors":"Chenchen Li, Mostafa Heidari Majd, Ameneh Heidari, Zohreh Razmara, Dongdong Guo","doi":"10.2174/0118715206380073250811113008","DOIUrl":"https://doi.org/10.2174/0118715206380073250811113008","url":null,"abstract":"<p><strong>Introduction: </strong>Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes may utilize this pathway to enhance transport efficiency.</p><p><strong>Methods: </strong>The Cu/Na dipicolinic acid complex was synthesized to assess its cytotoxicity, induction of apoptosis, drug resistance, and inflammation in cancerous and normal lung cells. The effects of oxidative stress on erythrocytes were also examined.</p><p><strong>Results: </strong>Cytotoxicity tests (MTT and SRB) showed superior inhibitory effects on A549 lung cancer cells compared to cisplatin, with no toxicity observed in MRC-5 normal lung fibroblast cells. Real-time PCR revealed increased caspase-3 expression (extrinsic apoptosis) for the complex compared to cisplatin, possibly due to CTR1- mediated entry. The complex did not induce drug resistance, as shown by AKT1 expression, and reduced TNF-α expression, preventing inflammation in normal cells. In contrast to cisplatin, the complex caused minimal oxidative stress in erythrocytes.</p><p><strong>Discussion: </strong>It can be concluded that the Cu/Na dipicolinic acid complex may be easily transported by CTR1 to malignant tumors, particularly lung cancer. This complex has the ability to inhibit cancer cell growth and induce apoptosis in lung cancer cells. Therefore, copper complexes show promise as potential therapeutic options for treating this type of cancer.</p><p><strong>Conclusion: </strong>The copper/sodium complex demonstrates enhanced therapeutic efficacy in lung cancer cells, requiring lower doses than cisplatin, while being safer for normal cells and erythrocytes.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013739","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":"Luteolin Enhances Anticancer Effects of PX-478 during Hypoxic Response in Metastatic Breast Cancer Cells.","authors":"Muzaffer Dukel, Fatema Zarzou","doi":"10.2174/0118715206384227250901064037","DOIUrl":"https://doi.org/10.2174/0118715206384227250901064037","url":null,"abstract":"<p><strong>Introduction: </strong>The presence of severe hypoxic stress can drive tumor growth, angiogenesis, and metastatic characteristics via up-regulated hypoxia-inducible factor 1-alpha (HIF-1α). Hence, targeting HIF-1α is considered a promising strategy, as increased HIF-1α activity is a key factor in the aggressive phenotype of malignancies. In this study, we aimed to investigate the anti-cancer effects of several flavonoids, both single and in combination with PX-478, in breast cancer cell lines.</p><p><strong>Methods: </strong>We tested the effects of luteolin and PX-478, both alone and in combination, on HIF-1α level in breast cancer cells under hypoxia using the cell viability assay. To determine the rationale for the cell growth inhibition induced by the luteolin+PX-478 combination, we conducted experiments to assess cell survival, apoptosis, cell cycle, invasion, and migration under both normoxic and hypoxic conditions. Furthermore, we evaluated the effect of this combination on DNA damage response under hypoxic stress via Comet assay and immunofluorescence staining.</p><p><strong>Results: </strong>Our findings revealed that the luteolin+PX-478 combination significantly suppressed the growth of MDA-MB-231 cells. In addition, we assessed time-dependent expression of HIF1α in MDA-MB-231 cells and observed that the combination of luteolin and PX-478 down-regulated the HIF-1α level. Finally, we found that the luteolin+PX-478 combination induced apoptosis and G2 cell cycle arrest and enhanced DNA damage response. This combination also sensitized breast cancer cells to ionizing radiation in hypoxic stress.</p><p><strong>Discussion: </strong>The findings suggested that targeting HIF-1α with a combination of luteolin and PX-478 may provide a synergistic approach to suppressing tumor growth and enhancing therapeutic response under hypoxic conditions. The observed effects on apoptosis, cell cycle arrest, and DNA damage response indicated that this combination could be a promising strategy for overcoming hypoxia-induced resistance in breast cancer therapy.</p><p><strong>Conclusion: </strong>Collectively, our results suggested the combination of luteolin and PX-478 to enhance the anticancer effects of PX-478 in breast carcinoma cells by impeding the cell growth and inducing DNA damage response under hypoxia.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013680","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":"Narrative Review Article A Comprehensive Review of the Anticancer Activity of Farnesiferol C and Umbelliferone.","authors":"Reyhane Faghih, Mehrshad Talebi-Esmaeilan, Seyed Mahdi Mohamadi-Zarch, Seyyed Majid Bagheri","doi":"10.2174/0118715206380074250829111459","DOIUrl":"https://doi.org/10.2174/0118715206380074250829111459","url":null,"abstract":"<p><p>Cancer remains a growing challenge in modern society, presenting a significant obstacle in both developed and developing countries. Conventional treatments are often costly and limited by issues such as drug resistance and undesirable side effects. Consequently, the exploration of natural compounds has emerged as a promising strategy for developing more effective and tolerable cancer therapies. Among these, Ferula plants have gained attention for their potential anticancer components. Notably, two coumarin compounds derived from these plants, farnesiferol C and umbelliferone, have demonstrated substantial anticancer activity, as supported by an increasing number of published studies. This review aims to consolidate existing evidence on the anticancer effects of farnesiferol C and umbelliferone while comparing their efficacy as potential therapeutic agents. To accomplish this, a comprehensive literature search was conducted using the terms \"umbelliferone\" and \"farnesiferol C\" paired with \"anticancer\" across databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Relevant studies up to March 2024 were retrieved, summarized, and incorporated into this analysis. The findings indicate that both compounds exhibit significant anticancer properties, positioning them as viable candidates for future drug development. A comparative analysis of their IC50 values, the concentration required to inhibit 50% of cancer cell growth, reveals that farnesiferol C demonstrates greater cytotoxic potency against various cancer cell lines compared to umbelliferone. However, while these results are encouraging, further research is recommended, particularly in vivo studies to evaluate the compounds' toxicity and therapeutic potential in living organisms.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999427","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":"Unlocking the Potential of Polysaccharides for the Treatment of Lung Cancer.","authors":"Himanshu Singh, Rajnish Kumar, Avijit Mazumder","doi":"10.2174/0118715206395910250816110857","DOIUrl":"https://doi.org/10.2174/0118715206395910250816110857","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer remains a leading cause of cancer-related deaths worldwide, with its incidence continuing to rise. Despite advancements in clinical treatments, their effectiveness is often restricted, emphasizing the need for novel therapeutic strategies. Natural products have long been explored for drug development, and among them, polysaccharides have gained significant attention due to their biocompatibility, biodegradability, and multiple biological functions.</p><p><strong>Methods: </strong>A comprehensive review examined contemporary research on the anticancer properties of natural polysaccharides, focusing specifically on their effects in lung cancer. The analysis included studies investigating their influence on cancer cell growth, immune system modulation, and therapeutic outcomes. Evidence from laboratory (in vitro), animal (in vivo), and clinical studies was evaluated to provide a comprehensive overview of their potential role in lung cancer management.</p><p><strong>Results: </strong>Findings from recent studies indicate that polysaccharides can effectively inhibit the proliferation of lung cancer cells, thereby slowing tumor development. These compounds also appear to enhance immune responses by activating various immune cells and regulating cytokine production. Furthermore, polysaccharides have been shown to positively affect the gut microbiota, which may contribute to improved drug efficacy and a reduction in resistance to chemotherapy.</p><p><strong>Discussion: </strong>The evidence suggests that natural polysaccharides exert multifaceted effects in the context of lung cancer treatment. Their ability to directly suppress tumor growth, modulate the immune system, and interact with the gut microbiome positions them as promising adjuncts to existing therapies. However, the precise molecular mechanisms underlying these effects are not yet fully understood, and variability in study designs warrants cautious interpretation of the results.</p><p><strong>Conclusion: </strong>Natural polysaccharides represent a promising complementary approach for lung cancer therapy, given their potential to inhibit tumor progression, enhance immune function, and improve the effectiveness of conventional drugs. Continued research is essential to fully elucidate their mechanisms of action and to translate these findings into effective clinical interventions.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999468","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":"Microbial-Derived Anti-Cancer Compounds: Advances in Drug Discovery, Bioengineering, and Therapeutic Applications.","authors":"Ekta Tyagi, Divya Jain, Rajabrata Bhuyan, Anand Prakash","doi":"10.2174/0118715206399680250814104403","DOIUrl":"https://doi.org/10.2174/0118715206399680250814104403","url":null,"abstract":"<p><strong>Introduction: </strong>Microbial metabolites represent a valuable source of bioactive compounds with promising anticancer properties. However, conventional drug discovery approaches are time-intensive and resource-demanding.</p><p><strong>Methods: </strong>Recent developments in artificial intelligence (AI), machine learning (ML), molecular docking, and quantitative structure-activity relationship (QSAR) modeling have been examined for their role in the identification and optimization of microbial metabolites.</p><p><strong>Results: </strong>AI-driven approaches have significantly enhanced compound screening and prediction of therapeutic efficacy. Nanocarrier-based drug delivery systems have improved the bioavailability, specificity, and stability of microbial metabolites while minimizing systemic toxicity. Despite these advancements, challenges remain in clinical translation due to the lack of in vivo validation and comprehensive pharmacokinetic data.</p><p><strong>Discussion: </strong>This review highlights the integration of advanced computational tools and nanotechnology in accelerating the discovery and delivery of microbial-derived anticancer agents.</p><p><strong>Conclusion: </strong>Future directions should focus on integrating AI with synthetic biology to engineer microbial strains capable of producing enhanced bioactive compounds. Additionally, leveraging nanotechnology could refine targeted delivery mechanisms. A deeper understanding of molecular pathways and drug resistance mechanisms is essential to support the development of combination therapies. Overall, microbialderived compounds hold substantial potential in advancing precision oncology.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999460","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":"Long Non-Coding RNA VPS9D1-AS1 in Human Cancer: Functions, Mechanisms, and Clinical Utility.","authors":"Jingjie Yang, Haodong He, Haoran Liu, Zhouya Xu, Li Li, Houdong Li, Chengfu Yuan","doi":"10.2174/0118715206400852250818061543","DOIUrl":"https://doi.org/10.2174/0118715206400852250818061543","url":null,"abstract":"<p><strong>Introduction: </strong>VPS9 domain-containing 1 antisense RNA 1 (VPS9D1-AS1), also known as c-Mycupregulated lncRNA (MYU) and FAK-interacting and stabilizing lncRNA (FAISL), is a novel long non-coding RNA (lncRNA) located at the human chromosome 16q24.3 locus. It has been reported to be highly expressed in various human cancers and associated with poor clinical pathological features and unfavorable prognosis in eight of the malignant tumors.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using PubMed, Web of Science, and Google Scholar databases to identify relevant articles on \"VPS9D1-AS1\", \"MYU\", or \"FAISL\". Only peer-reviewed publications were included, and articles related to oncology were specifically collected.</p><p><strong>Results: </strong>Mechanistically, VPS9D1-AS1 serves as a key regulator in four molecular models: signal, scaffold, guide, and decoy. These functions allow it to regulate the expression of target genes and activation of signaling pathways, thereby influencing the malignant phenotype of tumors.</p><p><strong>Discussion: </strong>The diverse molecular mechanisms of VPS9D1-AS1 highlight its significant role in the development and progression of various cancers. Its ability to act as a signal, scaffold, guide, and decoy suggests that it can influence multiple aspects of tumor biology, including proliferation, invasion, and metastasis.</p><p><strong>Conclusion: </strong>VPS9D1-AS1 plays a significant role in the development and progression of various cancers through its diverse molecular mechanisms. Further research on VPS9D1-AS1 may provide valuable insights, which may facilitate the development of new diagnostic and therapeutic strategies for cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999415","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":"Euxanthone Inhibits Hepatocellular Carcinoma Progression by Targeting the miR-199a-5p/E2F3 Regulatory Axis.","authors":"Ahmed Abdullah Al Awadh","doi":"10.2174/0118715206392043250805112033","DOIUrl":"https://doi.org/10.2174/0118715206392043250805112033","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths on a global scale. This study aimed to evaluate the effects of euxanthone on the proliferation of HCC cell lines and elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>HCC cell lines (HepG2, Huh-7, SNU-398, SK-HEP-1, Hep3B) and the normal liver cell line THLE-2 were cultured and treated with euxanthone at concentrations between 0 and 100 μM. Cell viability was evaluated using the MTT assay, while phase contrast microscopy and cell cycle analysis were performed to evaluate morphological changes and cell cycle distribution. qRT-PCR was utilized to measure miRNA and mRNA expression levels, while a dual luciferase reporter assay validated the interaction between miR-199a-5p and E2F3.</p><p><strong>Results: </strong>Euxanthone significantly (P < 0.05) inhibited cell proliferation in all HCC cell lines, with IC₂⁽ values between 6.25 and 25 μM. HepG2 cells exhibited pronounced sensitivity, with an IC₂⁽ of 6.25 μM. Euxanthone induced a G1 phase arrest, characterized by decreased expression of Cyclin D1 and E, and increased levels of p21. Additionally, it upregulated miR-199a-5p, which was identified as a mediator of the antiproliferative effects by targeting E2F3. Euxanthone treatment also significantly (P < 0.05) inhibited HepG2 cell migration in a wound healing assay.</p><p><strong>Conclusion: </strong>Taken together, euxanthone exerts antiproliferative effects on HCC cells via the miR-199a-5p-E2F3 axis and inhibits cell migration. These findings support its potential as a therapeutic agent for HCC, highlighting the need for further investigation into its clinical applications.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999404","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}