Current cancer drug targets最新文献

{"title":"Promotion of Melanoma Progression through MCM4-Induced Immune Suppression and Polarization of Macrophages by Carcinogenic Exosomes.","authors":"Xuewei Zhang, Sirong Liu, Deni Kang, Ronghua Yang","doi":"10.2174/0115680096357750250507073948","DOIUrl":"https://doi.org/10.2174/0115680096357750250507073948","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to provide a comprehensive understanding of the crucial role of MCM4 in melanoma progression regarding the regulatory communication between macrophages and cancer cells mediated by extracellular vesicles.</p><p><strong>Methods: </strong>Initially, a preliminary analysis was conducted using the Tumor Immune Estimation Resource (TIMER) database. Subsequently, the role of MCM4 knockdown on the polarization of THP- 1 and RAW264.7 macrophages was observed. Finally, the biological functionalities of exosomes derived from A375 cells overexpressing MCM4 on normal melanocytes (HEM-L) were explored.</p><p><strong>Results: </strong>On the one hand, MCM4 knockdown resulted in the upregulation of M1 macrophage markers and downregulation of M2 macrophage markers, indicating that MCM4 could facilitate polarization of macrophages toward the M2 phenotype and suggesting its oncogenic potential. On the other hand, MCM4 overexpression in melanocytes increased the secretion of exosomes, enhancing the proliferation, clonogenic, and DNA synthesis abilities of normal melanocytes. In addition, MCM4 overexpression-induced secretion of exosomes promoted the migration and invasion capabilities of normal melanocytes.</p><p><strong>Conclusion: </strong>Exosomes secreted by MCM4-overexpressed melanocytes could stimulate their proliferation, migration, and invasion abilities. MCM4 promoted M2 polarization of macrophages, indicating its crucial role in tumor microenvironment formation and thereby facilitating tumor development.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076562","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":"Advances and Future Prospects of Lipid-Based Nanocarriers in Targeted Cancer Therapy: A Comprehensive Review.","authors":"Suraj Mandal","doi":"10.2174/0115680096351325250412164059","DOIUrl":"https://doi.org/10.2174/0115680096351325250412164059","url":null,"abstract":"<p><strong>Introduction: </strong>Targeted cancer therapy has significantly transformed the field of oncology by improving treatment precision and reducing the occurrence of unintended side effects. Lipid-based nanocarriers have become a viable platform for delivering chemothera-peutic drugs due to their biocompatibility, flexibility, and ability to be functionalised.</p><p><strong>Aim and objectives: </strong>The objective of this research is to investigate the present tactics and future prospects of lipid-based nanocarriers in the field of targeted cancer treatment. The goals include the examination of recent progress in the development of lipid nanocarriers, evaluating their effectiveness in clinical uses, and pinpointing opportunities for enhancement and novelty.</p><p><strong>Material and method: </strong>An extensive literature analysis was performed, including examining current research on the use of lipid-based nanocarriers in cancer treatment. An analysis was conducted on data pertaining to nanocarrier formulations, targeting mechanisms, treatment results, and clinical trials in order to detect trends and new technologies.</p><p><strong>Results: </strong>Recent progress in lipid-based nanocarriers, including liposomes, solid lipid nano-particles, and nanoemulsions, has shown enhanced drug delivery and decreased toxicity. Targeting methods, such as the utilisation of ligand-receptor interactions and stimuli-responsive systems, have significantly improved the precision and effectiveness of therapeu-tics.</p><p><strong>Conclusion: </strong>Lipid-based nanocarriers have great potential for advancing targeted cancer treatment in the future. Although there has been significant progress, it is essential to con-tinue developing formulation processes and targeting tactics to overcome existing con-straints and improve clinical results. Ongoing cooperation across several fields of study will be crucial in effectively applying these nanotechnologies from the laboratory to practical use in healthcare.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076516","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":"Exploring the Role of Long Non-Coding RNAs in Mediating Cisplatin Resistance in Colorectal Cancer.","authors":"Shirin Azizidoost, Omid Anbiyaee, Atefeh Bahmani, Maryam Khombi Shooshtari, Pezhman Alavinejad, Sara Zarasvandnia, Maryam Farzaneh","doi":"10.2174/0115680096376480250408070103","DOIUrl":"https://doi.org/10.2174/0115680096376480250408070103","url":null,"abstract":"<p><p>Colorectal cancer (CRC) usually begins as adenomatous polyps in the colorectal or rectal epithelial cells. Currently, there are no reliable biomarkers for early CRC screening or prognostic prediction, leading to late-stage diagnoses when surgical options may no longer be viable. The disease is driven by mutations in oncogenes, tumor suppressor genes, and DNA repair genes, with rapid growth and metastasis contributing to treatment failure. Over the past two decades, research on non-coding RNAs (ncRNAs), particularly long ncRNAs (lncRNAs), has expanded significantly, revealing their critical roles in cancer biology. LncRNAs are involved in numerous biological processes such as cell proliferation, apoptosis, metabolism, and drug resistance, and they are often abnormally expressed in various cancers, including hepatocellular carcinoma, pancreatic cancer, and bladder cancer. In CRC, lncRNAs play a regulatory role by influencing cell cycle, proliferation, apoptosis, and epithelial-mesenchymal transition, and some have been shown to affect CRC cell proliferation, invasion, and resistance to cisplatin, highlighting their potential as therapeutic targets and biomarkers in cancer treatment. This review highlights current investigations on the functions and mechanisms of lncRNAs in cisplatin resistance in CRC. Such overview is anticipated to contribute to figuring out that lncRNAs can be applied as a promising target gene to develop drug resistance and remedial efficacy.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972300","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":"Promising Response to Pyrotinib in Non-Small-Cell Lung Cancer with the Rare HER2 R456C Mutation: A Case Report.","authors":"Yajie Wang, Jiaqi Hu, Runze Liu, Pei Li, Luokun Wang, Guangjian Yang","doi":"10.2174/0115680096371951250409093625","DOIUrl":"https://doi.org/10.2174/0115680096371951250409093625","url":null,"abstract":"<p><strong>Background: </strong>HER2 exon 20 insertions exhibit relative resistance to chemotherapy and covalent HER2-targeted tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). Furthermore, specific missense mutations in the extracellular domain of the HER2 protein have been identified as oncogenic drivers in NSCLC. However, their structural properties and clinical response to HER2-targeted inhibitors remain poorly understood, warranting further investigation. R456C represents a rare exon 12 missense mutation in the HER2 extracellular domain, with limited documentation in NSCLC.</p><p><strong>Case presentation: </strong>This study presents an atypical case of NSCLC with a HER2 R456C mutation, where the patient experienced a favorable response and substantial survival benefit from the HER2-targeted inhibitor pyrotinib. A patient, a 65-year-old man diagnosed with stage IIIB lung adenocarcinoma, initially underwent radical concurrent chemoradiotherapy. Upon disease recurrence, polymerase chain reaction assay detected no oncogenic alterations, and programmed cell death ligand 1 (PD-L1) expression was negative. Chemotherapy in combination with bevacizumab resulted in stable disease, providing a progression-free survival (PFS) benefit of 6 months. However, anlotinib proved ineffective against brain metastasis, necessitating brain radiotherapy. A subsequent lung biopsy confirmed adenocarcinoma and next-generation sequencing identified a somatic HER2 exon 12 missense mutation, p.R456C. Following pyrotinib administration, the patient's pulmonary metastases significantly diminished, and the brain metastasis regressed, resulting in a partial response and a PFS benefit of 13 months.</p><p><strong>Conclusion: </strong>To the best of our knowledge, this study represents the first reported case demonstrating the promising efficacy of pyrotinib in HER2-altered NSCLC harboring the ra-re exon 12 R456C mutation. Heterogeneous alterations in the HER2 extracellular segment, such as R456C, may be targetable and could confer survival benefits with HER2-targeted inhibitors.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995271","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 Association of KRAS and P53 Gene Mutations and MDM2 Expression with the Occurrence of Colorectal Cancer.","authors":"Hany A Al-Hussaniy, Amjad I Oraibi, Zahraa Salam Al-Tameemi, Ali Hikmat Alburghaif, Meena Akeel Naji, Fatima Akeel Naji","doi":"10.2174/0115680096349198250407100724","DOIUrl":"https://doi.org/10.2174/0115680096349198250407100724","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) encompasses various cancers located in the rectosigmoid junction, rectum, and anus, as well as parts of the colon. Globally, CRC is the second leading cause of cancer-related mortality and the third most prevalent malignan-cy. The KRAS oncogene was found to be mutated in 30 to 50% of CRC cases, leading to dysregulated cellular functions. Furthermore, the connection between KRAS and P53 gene mutations and the incidence of both colorectal and breast cancer remains an area of interest.</p><p><strong>Method: </strong>This comprehensive narrative review was carried out by mining data from recog-nized databases, such as PubMed, Google Scholar, and ResearchGate. The purpose was to extensively explore and understand the association between the KRAS and P53 gene muta-tions and the prevalence of colorectal and breast cancers.</p><p><strong>Results: </strong>The mutation in the KRAS oncogene has been identified as a key player in cellular signaling pathways, including MAPK, PI3K, and PLD. Despite extensive research, gene therapies targeting these mutations have seen limited success, especially in codons 12, 13, 61, and 143.</p><p><strong>Conclusion: </strong>Mutations in the KRAS and P53 genes, along with aberrant MDM2 expression, play pivotal roles in the onset and progression of colorectal cancer by disrupting key cellular signaling pathways, such as MAPK, PI3K, and PLD. Despite advancements in understand-ing these mechanisms, current gene therapy approaches have shown limited success, particu-larly in targeting KRAS codon mutations. This underscores the urgent need for innovative therapeutic strategies and further research to develop effective treatments for colorectal can-cer and its potential links to other malignancies, such as breast cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972710","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":"Exosome-mediated Induction of Apoptosis in Cisplatin-treated Gastric Cancer Cells as a Strategy to Mitigate Side Effects.","authors":"Jiaqi Zhu, Hui Wang, Yijie Liu, Wen Li, Li Cao, Wenjing Wang, Suoni Li, Jin Shang, Yannan Qin, Chen Huang, Bo Guo","doi":"10.2174/0115680096369817250407164352","DOIUrl":"https://doi.org/10.2174/0115680096369817250407164352","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer is the third most lethal malignancy worldwide. While cisplatin has shown remarkable efficacy at a low cost, it is also associated with severe side effects. Exosomes play a key role in mediating the bystander effect of radiation and have the capacity to deliver apoptosis signals for targeted destruction of tumor cell. However, there remains a paucity of research on exosome-mediated bystander effects in the context of chemotherapeutic drugs.</p><p><strong>Objective: </strong>This study aims to investigate the ability of cisplatin-induced exosomes to deliver apoptosis signals to gastric cancer cells, with the aim of mitigating the adverse effects associated with chemotherapy.</p><p><strong>Methods: </strong>Differential ultracentrifugation was used to isolate apoptotic exosomes secreted by cisplatin-induced gastric cancer MKN-28 cells. Characterization and identification of these exosomes were performed by transmission electron microscopy, particle size analyzer, flow cytometry, and Western blotting. The transduction efficiency of the exosomes was confirmed through immunefluorescence. The effects of apoptotic exosomes on the proliferation, apoptosis, migration, cycle, senescence, and tumor formation of MKN-28 cells in vitro and in vivo were investigated by live cell workstation, flow cytometry, HE staining, and tumor-igenicity assays.</p><p><strong>Results: </strong>Cisplatin-induced apoptotic exosomes, termed DDP-EXO, exhibited a significantly enhanced inhibitory effect on the proliferation of MKN-28 cells compared to gastric epithelial GES-1 cells. Moreover, DDP-EXO was able to deliver apoptotic signals to MKN-28 cells, leading to an increase in the apoptotic population in recipient cells, possibly through the involvement of Caspase-9. Furthermore, DDP-EXO showed limited impacts on cell migration, cell cycle, or cell senescence. In vivo, DDP-EXO effectively suppressed tumorigenesis in a subcutaneous tumor model without causing detectable pathological changes in main organs and blood samples, suggesting a favorable safety profile.</p><p><strong>Conclusion: </strong>In summary, this study provides new perspectives on the potential application of exosomes as an innovative therapeutic approach for gastric cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992997","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":"MND1 Promotes the Proliferation of Prostate Cancer Cell via the CCNB1/p53 Signaling Pathway.","authors":"Zhongxiang Zhao, Yesong Zou, Qian Lv, Chenxiao Wu, Ke Tang, Fazhong Dai, Jiayao Feng, Hongshen Lai, Wenjie Lai, Xiaofu Qiu","doi":"10.2174/0115680096391591250506064859","DOIUrl":"https://doi.org/10.2174/0115680096391591250506064859","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PCa) is one of the most commonly diagnosed can-cers in men, with a high global incidence. The Meiotic Nuclear Division 1 (MND1) protein is essential for the repair of DNA double-strand breaks during meiosis, but its role in PCa re-mains poorly understood. This study aims to explore the function of MND1 in PCa progression and the mechanism involved.</p><p><strong>Methods: </strong>RNA-Seq data from the TCGA and GEO databases were analyzed. Kaplan-Meier (KM) method and χ2 test examined the association between MND1 expression, prognosis, and clinical parameters. PCa cell lines (22RV1 and C4-2) were used for functional assays. CCK-8, EdU, colony formation assay, flow cytometry analysis and xenograft model were used to evaluate the effects of MND1 on PCa cell proliferation in vitro and in vivo.</p><p><strong>Results: </strong>MND1 expression was significantly upregulated in PCa tissues, particularly in cases with Gleason scores ≥8, and correlated with poorer disease-free survival (DFS) and adverse clinical features. Functionally, elevated MND1 expression promoted PCa cell proliferation both in vitro and in vivo. Mechanistically, MND1 facilitated cell cycle progression from G0/G1 to S phase via activation of the CCNB1/p53 signaling pathway.</p><p><strong>Conclusion: </strong>MND1 promotes prostate cancer progression by facilitating the G0/G1 to S phase transition via the CCNB1/p53 pathway, making it a promising prognostic marker and potential therapeutic target.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966924","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":"CREC Family Genes as Biomarkers and Therapeutic Targets in Lung Adenocarcinoma: In vitro and In silico Insights.","authors":"Yimin Jiang, Guangfu Zhu, Xueqin Cheng, Xinyue Mo, Yi Chen, Fengqi Xu, MeiFang Wang, Yijun Tang","doi":"10.2174/0115680096363759250401045735","DOIUrl":"https://doi.org/10.2174/0115680096363759250401045735","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC), characterized by poor prognosis and limited treatment options.</p><p><strong>Material and methods: </strong>This study investigated the expression patterns and functional roles of the CREC family genes (RCN1, RCN2, RCN3, SDF2, and CALU) in LUAD using vari-ous detailed molecular and in silico experiments.</p><p><strong>Results: </strong>RT-qPCR analysis revealed significant upregulation of all five genes in LUAD cell lines compared to normal controls, with ROC curve analysis suggesting their potential as di-agnostic biomarkers. Validation using independent datasets (Oncomine, UALCAN, and HPA) confirmed these findings at both the transcript and protein levels. Stage-specific ex-pression and promoter methylation analyses demonstrated that RCN1 and CALU exhibit higher expression in advanced stages, while promoter hypomethylation correlated with gene overexpression in LUAD. Mutation and copy number variation (CNV) analyses indicated that CREC gene alterations are common in LUAD, with CALU and RCN3 frequently mu-tated. Functional assays revealed that knockdown of SDF2 and CALU significantly reduced cell proliferation, colony formation, and wound healing abilities in A549 cells, suggesting their roles in promoting LUAD progression. Gene enrichment and miRNA interaction anal-yses highlighted the involvement of CREC genes in processes like calcium binding, oxida-tive stress response, and immune regulation. CALU emerged as a potential prognostic mark-er, showing a significant association with poorer survival outcomes.</p><p><strong>Conclusion: </strong>Together, the findings of this study suggested that CREC family genes may serve as promising diagnostic and therapeutic targets in LUAD.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981690","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":"Ergodic Manipulation of Genome Chaos: Innovative Strategies against Malignant Progression.","authors":"Sergey Shityakov, Viacheslav Kravtsov","doi":"10.2174/0115680096379988250415094558","DOIUrl":"https://doi.org/10.2174/0115680096379988250415094558","url":null,"abstract":"<p><p>Genome instability is a key driver of malignant progression in cancer and is char-acterized by chromoanagenesis, including spontaneous events, such as chromothripsis, chromoanasynthesis, and chromoplexy. These genome catastrophes create the heterogeneity necessary for tumor cells to adapt, evolve, and resist therapy. Ergodic anticancer therapy rep-resents a novel strategy for targeting cancer stem cells by manipulating their genome chaos. Two approaches have been proposed: ergodynamic anticancer therapy (EDAT), which en-hances genome chaos beyond a critical threshold and leads to self-destruction, and ergostatic anticancer therapy (ESAT), which suppresses chaos and limits malignant progression. This brief review explores the conceptual foundations, molecular mechanisms, and therapeutic potential of ergostatic and ergodynamic therapies in treating cancer, highlighting their role in personalized medicine.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970278","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":"Arctigenin Suppresses Melanoma via Mitophagy Activation In vitro and Enhances Dacarbazine Sensitivity In vivo.","authors":"Ling Jiang, Yang Lu, Hongyan Zhao, Weiyang He","doi":"10.2174/0115680096373796250414062644","DOIUrl":"https://doi.org/10.2174/0115680096373796250414062644","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the effect and mechanism of arctigenin (ARG) on the sensitization of dacarbazine (DTIC) via the regulation of mitophagy.</p><p><strong>Methods: </strong>In vitro experiments were conducted to explore the effects of ARG on the biologi-cal behavior of melanoma cells, mitochondrial autophagy mediated by PINK1/Parkin, and the role of reactive oxygen species (ROS)-mitochondrial autophagy in the regulation of the biological behavior of melanoma cells by an ROS quenching agent, a mitochondrial autoph-agy inhibitor, and an activator. The effects of ARG and dacarbazine in nude mice were as-sessed.</p><p><strong>Results: </strong>CCK8 assays revealed that ARG inhibited the proliferation of the human melanoma cell lines A375 and SK-MEL-2. The observation of submicroscopic structures demonstrated mitochondrial damage. Flow cytometry further verified that ARG induced apoptosis. West-ern blot analysis revealed that the protein expression levels of cleaved caspase 3 and Bax in-creased, whereas that of Bcl-2 decreased. In addition, ARG increased ROS levels. LC3II/I, PINK1, and Parkin were increased. ARG-induced apoptosis was related to increased mito-chondrial oxidative stress and promoted the occurrence of mitochondrial autophagy. After the addition of the autophagy inhibitor Mdivi-1 or the ROS quencher N-acetylcysteine (NAC), the antiproliferative effect of ARG was markedly attenuated. The expression levels of PINK1, Parkin, LC3II/I, cleaved caspase 3, and Bax were increased, whereas that of Bcl-2 was decreased. The formation of mitochondrial autophagosomes was observed by transmis-sion electron microscopy. ARG inhibited the proliferation and induced the apoptosis of mel-anoma cells in vivo.</p><p><strong>Conclusion: </strong>Autophagy-mediated cell apoptosis was activated through the PINK1/Parkin pathway by ARG, effectively inhibiting the proliferation of human melanoma cells.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978486","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}