Apoptosis最新文献

{"title":"Strong activation of p53 by actinomycin D and nutlin-3a overcomes the resistance of cancer cells to the pro-apoptotic activity of the FAS ligand","authors":"Barbara Łasut-Szyszka,&nbsp;Agnieszka Gdowicz-Kłosok,&nbsp;Małgorzata Krześniak,&nbsp;Magdalena Głowala-Kosińska,&nbsp;Agnieszka Będzińska,&nbsp;Marek Rusin","doi":"10.1007/s10495-024-02000-0","DOIUrl":"10.1007/s10495-024-02000-0","url":null,"abstract":"<div><p>The FAS ligand (FASLG) is expressed on lymphocytes, which employ it to activate death receptors on target cells. Cancer cells are generally resistant to apoptosis triggered by FASLG. In this work, we found a way to circumvent this resistance by treatment with actinomycin D (ActD) and nutlin-3a (Nut3a). We selected this drug combination based on our transcriptomic data showing strong activation of proapoptotic genes, including those for receptor-mediated apoptosis, in cells exposed to actinomycin D and nutlin-3a. To test our hypothesis, we pre-exposed cancer cell lines to this drug combination for 45 h and then treated them with recombinant FASLG. This almost instantaneously killed most cells. Actinomycin D and nutlin-3a strongly cooperated in the sensitization because the effect of the drugs acting solo was not as spectacular as the drug combination, which together with FASLG killed more than 99% of cells. Based on the caspase activation pattern (caspase-8, caspase-9, caspase-10), we conclude that both extrinsic and intrinsic pro-apoptotic pathways were engaged. In engineered p53-deficient cells, this pro-apoptotic effect was completely abrogated. Therefore, the combination of ActD + Nut3a activates p53 in an extraordinary way, which overcomes the resistance of cancer cells to apoptosis triggered by FASLG. Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112, and actinomycin D + idasanutlin had a similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD + Nut3a + FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1515 - 1528"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-02000-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamine deprivation in glioblastoma stem cells triggers autophagic SIRT3 degradation to epigenetically restrict CD133 expression and stemness","authors":"Zhengcao Xing,&nbsp;Xianguo Jiang,&nbsp;Yalan Chen,&nbsp;Tiange Wang,&nbsp;Xiaohe Li,&nbsp;Xiangyun Wei,&nbsp;Qiuju Fan,&nbsp;Jie Yang,&nbsp;Hongmei Wu,&nbsp;Jinke Cheng,&nbsp;Rong Cai","doi":"10.1007/s10495-024-02003-x","DOIUrl":"10.1007/s10495-024-02003-x","url":null,"abstract":"<div><p>Glioblastoma multiforme (GBM) is a highly malignant brain tumor, and glioblastoma stem cells (GSCs) are the primary cause of GBM heterogeneity, invasiveness, and resistance to therapy. Sirtuin 3 (SIRT3) is mainly localized in the mitochondrial matrix and plays an important role in maintaining GSC stemness through cooperative interaction with the chaperone protein tumor necrosis factor receptor-associated protein 1 (TRAP1) to modulate mitochondrial respiration and oxidative stress. The present study aimed to further elucidate the specific mechanisms by which SIRT3 influences GSC stemness, including whether SIRT3 serves as an autophagy substrate and the mechanism of SIRT3 degradation. We first found that SIRT3 is enriched in CD133⁺ GSCs. Further experiments revealed that in addition to promoting mitochondrial respiration and reducing oxidative stress, SIRT3 maintains GSC stemness by epigenetically regulating CD133 expression <i>via</i> succinate. More importantly, we found that SIRT3 is degraded through the autophagy–lysosome pathway during GSC differentiation into GBM bulk tumor cells. GSCs are highly dependent on glutamine for survival, and in these cells, we found that glutamine deprivation triggers autophagic SIRT3 degradation to restrict CD133 expression, thereby disrupting the stemness of GSCs. Together our results reveal a novel mechanism by which SIRT3 regulates GSC stemness. We propose that glutamine restriction to trigger autophagic SIRT3 degradation offers a strategy to eliminate GSCs, which combined with other treatment methods may overcome GBM resistance to therapy as well as relapse.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1619 - 1631"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sphingolipid metabolism and regulated cell death in malignant melanoma","authors":"Kexin Yan,&nbsp;Wei Zhang,&nbsp;Hao Song,&nbsp;Xiulian Xu","doi":"10.1007/s10495-024-02002-y","DOIUrl":"10.1007/s10495-024-02002-y","url":null,"abstract":"<div><p>Malignant melanoma (MM) is a highly invasive and therapeutically resistant skin malignancy, posing a significant clinical challenge in its treatment. Programmed cell death plays a crucial role in the occurrence and progression of MM. Sphingolipids (SP), as a class of bioactive lipids, may be associated with many kinds of diseases. SPs regulate various forms of programmed cell death in tumors, including apoptosis, necroptosis, ferroptosis, and more. This review will delve into the mechanisms by which different types of SPs modulate various forms of programmed cell death in MM, such as their regulation of cell membrane permeability and signaling pathways, and how they influence the survival and death fate of MM cells. An in-depth exploration of the role of SPs in programmed cell death in MM aids in unraveling the molecular mechanisms of melanoma development and holds significant importance in developing novel therapeutic strategies.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"1860 - 1878"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD8 + CD103 + iTregs protect against ischemia-reperfusion-induced acute kidney Injury by inhibiting pyroptosis","authors":"Qiuju Chen,&nbsp;Xiao Zhang,&nbsp;Hui Yang,&nbsp;Guangxuan Luo,&nbsp;Xin Zhou,&nbsp;Zhenjian Xu,&nbsp;Anping Xu","doi":"10.1007/s10495-024-02001-z","DOIUrl":"10.1007/s10495-024-02001-z","url":null,"abstract":"<div><p>The occurrence of acute kidney injury (AKI) is elevated, one of the main causes is ischemia-reperfusion (I/R). However, no specific therapy is currently available to treat I/R-induced AKI (I/R-AKI). Treg cells have been demonstrated to perform an anti-inflammatory role in a range of autoimmune and inflammatory illnesses. However, there is limited available information about the possible functions of CD8 + CD103 + iTregs in I/R-AKI. We utilized renal tubular epithelial cells (RTECs) subjected to hypoxia-reoxygenation (H/R) and I/R-AKI mouse model to investigate whether CD8 + CD103 + iTregs could attenuate AKI and the underlying mechanism. In vitro, co-cultured with CD8 + CD103 + iTregs alleviated H/R-induced cell injury. After treatment of CD8 + CD103 + iTregs rather than control cells, a significant improvement of I/R-AKI was observed in vivo, including decreased serum creatinine (sCr) and blood urea nitrogen (BUN) levels, reduced renal pathological injury, lowered tubular apoptosis and inhibition of the transition from AKI to chronic kidney disease (CKD). Mechanically, CD8 + CD103 + iTregs alleviated H/R-induced cell injury and I/R-AKI partly by suppressing RTECs pyroptosis via inhibiting the NLRP3/Caspase-1 axis. Our study provides a novel perspective on the possibility of CD8 + CD103 + iTregs for the treatment of I/R-AKI.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1709 - 1722"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTGR1-mediated immune evasion mechanisms in late-stage triple-negative breast cancer: mechanisms of M2 macrophage infiltration and CD8+ T cell suppression","authors":"Fang Huang,&nbsp;Fuhe Wang,&nbsp;Qilu Hu,&nbsp;Ying Li,&nbsp;Da Jiang","doi":"10.1007/s10495-024-01991-0","DOIUrl":"10.1007/s10495-024-01991-0","url":null,"abstract":"<div><p>Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by metabolic dysregulation. Tumor cell immune escape plays an indispensable role in the development of TNBC tumors. Furthermore, in the abstract, we explicitly mention the techniques used and enhance the clarity and impact of our findings. “Based on bioinformatics analysis results, we utilized CRISPR/Cas9 technology to knockout the target gene and established a mouse model of breast cancer. Through experiments such as CCK8, scratch assay, and Transwell assay, we further investigated the impact of target gene knockout on the malignant behavior of tumor cells. Subsequently, we conducted immunohistochemistry and Western Blot experiments to study the expression of macrophage polarization and infiltration-related markers and evaluate the effect of the target gene on macrophage polarization. Next, through co-culture experiments, we simulated the tumor microenvironment and used immunohistochemistry staining to observe and analyze the distribution and activation status of M2 macrophages and CD8⁺ T cells in the co-culture system. We validated in vivo experiments the molecular mechanism by which the target gene regulates immune cell impact on TNBC progression.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"2002 - 2024"},"PeriodicalIF":6.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-01991-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The resistance to anoikis, mediated by Spp1, and the evasion of immune surveillance facilitate the invasion and metastasis of hepatocellular carcinoma","authors":"Zhengwei Zhang,&nbsp;Xiaoning Chen,&nbsp;Yapeng Li,&nbsp;Feng Zhang,&nbsp;Zhen Quan,&nbsp;Zhuo Wang,&nbsp;Yang Yang,&nbsp;Wei Si,&nbsp;Yuting Xiong,&nbsp;Jiaming Ju,&nbsp;Yu Bian,&nbsp;Shibo Sun","doi":"10.1007/s10495-024-01994-x","DOIUrl":"10.1007/s10495-024-01994-x","url":null,"abstract":"<div><p>Anoikis-Related Genes (ARGs) lead to the organism manifesting resistance to anoikis and are associated with unfavorable prognostic outcomes across various malignancies.Therefore, it is crucial to identify the pivotal target genes related to anoikis in HCC .We found that ARGs were significantly correlated with prognosis and immune responses in HCC. The core gene, SPP1, notably promoted anoikis resistance and metastasis in HCC through both in vivo and in vitro studies. The PI3K-Akt-mTOR pathway played a critical role in anoikis suppression within HCC contexts. Our research unveiled SPP1’s role in enhancing PKCα phosphorylation, which in turn activated the PI3K-Akt-mTOR cascade. Additionally, SPP1 was identified as a key regulator of MDSCs and Tregs migration, directly affecting their immunosuppressive capabilities.These findings indicate that in HCC, SPP1 promoted anoikis resistance and facilitated immune evasion by modulating MDSCs and Tregs.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1564 - 1583"},"PeriodicalIF":6.1,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-024-01994-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications","authors":"Xiaozhong Li,&nbsp;Zheng Zhou,&nbsp;Yu Tao,&nbsp;Lei He,&nbsp;Fenfang Zhan,&nbsp;Juxiang Li","doi":"10.1007/s10495-024-01999-6","DOIUrl":"10.1007/s10495-024-01999-6","url":null,"abstract":"<div><p>Homocysteine (Hcy) is a metabolic intermediate product derived from methionine. Hyperhomocysteinemia is a condition associated with various diseases. Hcy is recognized as a risk factor for cardiovascular disease (CVD). Ferroptosis, a novel form of cell death, is primarily characterized by substantial iron accumulation and lipid peroxidation. Recent research indicates a close association between ferroptosis and the pathophysiological processes of tumors, neurological diseases, CVD, and other ailments. However, limited research has been conducted on the impact of Hcy on ferroptosis. Therefore, this paper aimed to investigate the potential roles and mechanisms of homocysteine and ferroptosis in the context of cardiovascular disease. By conducting comprehensive literature research and analysis, we aimed to summarize recent advancements in understanding the effects of homocysteine on ferroptosis in cardiovascular diseases. This research contributes to a profound understanding of this critical domain.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"1944 - 1958"},"PeriodicalIF":6.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: ICB3E induces iNOS expression by ROS-dependent JNK and ERK activation for apoptosis of leukemic cells","authors":"Nabendu Biswas,&nbsp;Sanjit K. Mahato,&nbsp;Avik Acharya Chowdhury,&nbsp;Jaydeep Chaudhuri,&nbsp;Anirban Manna,&nbsp;Jayaraman Vinayagam,&nbsp;Sourav Chatterjee,&nbsp;Parasuraman Jaisankar,&nbsp;Utpal Chaudhuri,&nbsp;Santu Bandyopadhyay","doi":"10.1007/s10495-024-02007-7","DOIUrl":"10.1007/s10495-024-02007-7","url":null,"abstract":"","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1290 - 1290"},"PeriodicalIF":6.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol suppresses liver cancer progression by downregulating AKR1C3: targeting HCC with HSA nanomaterial as a carrier to enhance therapeutic efficacy","authors":"Ying Wang,&nbsp;Longxiang Su,&nbsp;Zhansheng Hu,&nbsp;Shuang Peng,&nbsp;Na Li,&nbsp;Haiyan Fu,&nbsp;Baoquan Wang,&nbsp;Huiping Wu","doi":"10.1007/s10495-024-01995-w","DOIUrl":"10.1007/s10495-024-01995-w","url":null,"abstract":"&lt;div&gt;&lt;p&gt;The enzyme AKR1C3 plays a crucial role in hormone and drug metabolism and is associated with abnormal expression in liver cancer, leading to tumor progression and poor prognosis. Nanoparticles modified with HSA can modulate the tumor microenvironment by enhancing photodynamic therapy to induce apoptosis in tumor cells and alleviate hypoxia. Therefore, exploring the potential regulatory mechanisms of resveratrol on AKR1C3 through the construction of HSA-RSV NPs carriers holds significant theoretical and clinical implications for the treatment of liver cancer. The aim of this study is to investigate the targeted regulation of AKR1C3 expression through the loading of resveratrol (RSV) on nanomaterials HSA-RSV NPs (Nanoparticles) in order to alleviate tumor hypoxia and inhibit the progression of hepatocellular carcinoma (HCC), and to explore its molecular mechanism. PubChem database and PharmMapper server were used to screen the target genes of RSV. HCC-related differentially expressed genes (DEGs) were analyzed through the GEO dataset, and relevant genes were retrieved from the GeneCards database, resulting in the intersection of the three to obtain candidate DEGs. GO and KEGG enrichment analyses were performed on the candidate DEGs to analyze the potential cellular functions and molecular signaling pathways affected by the main target genes. The cytohubba plugin was used to screen the top 10 target genes ranked by Degree and further intersected the results of LASSO and Random Forest (RF) to obtain hub genes. The expression analysis of hub genes and the prediction of malignant tumor prognosis were conducted. Furthermore, a pharmacophore model was constructed using PharmMapper. Molecular docking simulations were performed using AutoDockTools 1.5.6 software, and ROC curve analysis was performed to determine the core target. In vitro cell experiments were carried out by selecting appropriate HCC cell lines, treating HCC cells with different concentrations of RSV, or silencing or overexpressing AKR1C3 using lentivirus. CCK-8, clone formation, flow cytometry, scratch experiment, and Transwell were used to measure cancer cell viability, proliferation, migration, invasion, and apoptosis, respectively. Cellular oxygen consumption rate was analyzed using the Seahorse XF24 analyzer. HSA-RSV NPs were prepared, and their characterization and cytotoxicity were evaluated. The biological functional changes of HCC cells after treatment were detected. An HCC subcutaneous xenograft model was established in mice using HepG2 cell lines. HSA-RSV NPs were injected via the tail vein, with a control group set, to observe changes in tumor growth, tumor targeting of NPs, and biological safety. TUNEL, Ki67, and APC-hypoxia probe staining were performed on excised tumor tissue to detect tumor cell proliferation, apoptosis, and hypoxia. Lentivirus was used to silence or overexpress AKR1C3 simultaneously with the injection of HSA-RSV NPs via the tail vein to assess the i","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1429 - 1453"},"PeriodicalIF":6.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cuproptosis and Cu: a new paradigm in cellular death and their role in non-cancerous diseases","authors":"Zhibo Yang,&nbsp;Ridong Feng,&nbsp;Hai Zhao","doi":"10.1007/s10495-024-01993-y","DOIUrl":"10.1007/s10495-024-01993-y","url":null,"abstract":"<div><p>Cuproptosis, a newly characterized form of regulated cell death driven by copper accumulation, has emerged as a significant mechanism underlying various non-cancerous diseases. This review delves into the complex interplay between copper metabolism and the pathogenesis of conditions such as Wilson’s disease (WD), neurodegenerative disorders, and cardiovascular pathologies. We examine the molecular mechanisms by which copper dysregulation induces cuproptosis, highlighting the pivotal roles of key copper transporters and enzymes. Additionally, we evaluate the therapeutic potential of copper chelation strategies, which have shown promise in experimental models by mitigating copper-induced cellular damage and restoring physiological homeostasis. Through a comprehensive synthesis of recent advancements and current knowledge, this review underscores the necessity of further research to translate these findings into clinical applications. The ultimate goal is to harness the therapeutic potential of targeting cuproptosis, thereby improving disease management and patient outcomes in non-cancerous conditions associated with copper dysregulation.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 9-10","pages":"1330 - 1360"},"PeriodicalIF":6.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}