Apoptosis最新文献

{"title":"Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications.","authors":"Xiaozhong Li, Zheng Zhou, Yu Tao, Lei He, Fenfang Zhan, Juxiang Li","doi":"10.1007/s10495-024-01999-6","DOIUrl":"10.1007/s10495-024-01999-6","url":null,"abstract":"<p><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>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","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":"BH3-mimetics or DNA-damaging agents in combination with RG7388 overcome p53 mutation-induced resistance to MDM2 inhibition.","authors":"N V Pervushin, D K Nilov, S V Pushkarev, V O Shipunova, A S Badlaeva, M A Yapryntseva, D V Kopytova, B Zhivotovsky, G S Kopeina","doi":"10.1007/s10495-024-02014-8","DOIUrl":"10.1007/s10495-024-02014-8","url":null,"abstract":"<p><p>The development of drug resistance reduces the efficacy of cancer therapy. Tumor cells can acquire resistance to MDM2 inhibitors, which are currently under clinical evaluation. We generated RG7388-resistant neuroblastoma cells, which became more proliferative and metabolically active and were less sensitive to DNA-damaging agents in vitro and in vivo, compared with wild-type cells. The resistance was associated with a mutation of the p53 protein (His193Arg). This mutation abated its transcriptional activity via destabilization of the tetrameric p53-DNA complex and was observed in many cancer types. Finally, we found that Cisplatin and various BH3-mimetics could enhance RG7388-mediated apoptosis in RG7388-resistant neuroblastoma cells, thereby partially overcoming resistance to MDM2 inhibition.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103751","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":"Ferroptosis crosstalk in anti-tumor immunotherapy: molecular mechanisms, tumor microenvironment, application prospects.","authors":"Yining Lu, Xiaoting Xie, Lianxiang Luo","doi":"10.1007/s10495-024-01997-8","DOIUrl":"10.1007/s10495-024-01997-8","url":null,"abstract":"<p><p>Immunotherapies for cancer, specifically immune checkpoint inhibition (ICI), have shown potential in reactivating the body's immune response against tumors. However, there are challenges to overcome in addressing drug resistance and improving the effectiveness of these treatments. Recent research has highlighted the relationship between ferroptosis and the immune system within immune cells and the tumor microenvironment (TME), suggesting that combining targeted ferroptosis with immunotherapy could enhance anti-tumor effects. This review explores the potential of using immunotherapy to target ferroptosis either alone or in conjunction with other therapies like immune checkpoint blockade (ICB) therapy, radiotherapy, and nanomedicine synergistic treatments. It also delves into the roles of different immune cell types in promoting anti-tumor immune responses through ferroptosis. Together, these findings provide a comprehensive understanding of synergistic immunotherapy focused on ferroptosis and offer innovative strategies for cancer treatment.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615815","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":"Novel CAR-T cells targeting TRKB for the treatment of solid cancer.","authors":"Dandan Liang, Jie Tang, Bin Sun, Shuai He, Dong Yang, Haiyan Ma, Yuncang Yun, Yongjie Zhu, Wenwen Wei, Haiyang Chen, Xudong Zhao","doi":"10.1007/s10495-024-01936-7","DOIUrl":"10.1007/s10495-024-01936-7","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating blood cancers such as B-cell malignancies, however, its effectiveness as an approach to treat solid tumors remains to be further explored. Here, we focused on the development of CAR-T cell therapies targeting tropomyosin-related kinase receptor B (TRKB), a highly expressed protein that is significantly associated with tumor progression, malignancy, and drug resistance in multiple forms of aggressive solid tumors. To achieve this, we screened brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NTF4) ligand-based CAR-T cells for their efficiency in targeting the TRKB receptor in the context of solid tumors, particularly hepatocellular carcinoma and pancreatic cancer. We demonstrated that TRKB is overexpressed not only in hepatocellular carcinoma and pancreatic carcinoma cell lines but also in cancer stem-like cells (CSCs). Notably, BDNF-CAR T and NTF4-CAR T cells could not only effectively target and kill TRKB-expressing pan-cancer cell lines in a dose-dependent manner but also effectively kill CSCs. We also performed in vivo studies to show that NTF4-CAR T cells have a better potential to inhibit the tumor growth of hepatocellular carcinoma xenografts in mice, compared with BDNF-CAR T cells. Taken together, our findings suggest that CAR-T targeting TRKB may be a promising approach for developing novel therapies to treat solid cancers.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157439","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":"5-Aminolevulinic acid-mediated photodynamic therapy in combination with kinase inhibitor lapatinib enhances glioblastoma cell death.","authors":"Sharayu Chandratre, Daniel Merenich, Kenneth Myers, Bin Chen","doi":"10.1007/s10495-024-02012-w","DOIUrl":"10.1007/s10495-024-02012-w","url":null,"abstract":"<p><p>5-Aminolevulinic acid (ALA) is an intraoperative imaging agent approved for protoporphyrin IX (PpIX) fluorescence-guided resection of glioblastoma (GBM). It is currently under clinical evaluation for photodynamic therapy (PDT) after the completion of GBM surgery. We previously showed that lapatinib, a clinical kinase inhibitor of epidermal growth factor receptor 1 & 2 (EGFR and HER2), enhanced PpIX fluorescence in a panel of GBM cell lines by blocking ABCG2 (ATP-binding cassette super-family G member 2)-mediated PpIX efflux, which suggests its potential for improving ALA for GBM surgery and PDT. Here we show that lapatinib enhanced PDT-induced cytotoxicity by promoting GBM cell death with the induction of apoptosis followed by necrosis. While the induction of tumor cell apoptosis was massive and rapid in the H4 cell line with no detectable Bcl-2 and a low level of Bcl-xL, it was delayed and much less in extent in A172, U-87 and U-118 cell lines with higher levels of pro-survival Bcl-2 family proteins. Lapatinib treatment alone neither reduced GBM cell viability nor had any significant effect on EGFR downstream signaling. Its enhancement of ALA-PDT was largely due to the increase of intracellular PpIX particularly in the mitochondria, resulting in the activation of mitochondria-mediated apoptosis in H4 cells. Our present study demonstrates that lapatinib inhibits ABCG2-mediated PpIX efflux and sensitizes GBM cells to ALA-PDT by inducing tumor cell death.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071804","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":"Is long-term administration of PLD-pegylated liposomal doxorubicin able to induce oral cancer?","authors":"Arjun Pandian, Azhagu Madhavan Sivalingam","doi":"10.1007/s10495-024-02017-5","DOIUrl":"10.1007/s10495-024-02017-5","url":null,"abstract":"<p><p>Leukoplakia, a potentially malignant oral condition, manifests as a nonremovable white lesion that is often linked to risk factors such as smoking, alcohol, and HPV. Pegylated liposomal doxorubicin (PLD), which is used in cancer treatment, has been associated with secondary oral cancers, particularly in patients with leukoplakia. A case study revealed the development of squamous cell carcinoma (SCC) on the tongue following PLD treatment, suggesting a potential link between the drug and malignant transformation. Despite the benefits of PLD in reducing cardiac toxicity, long-term oral monitoring is essential due to the persistent risk of oral cancer posttreatment.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144994","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":"Targeted delivery of FAK siRNA by engineered exosomes to reverse cetuximab resistance via activating paraptosis in colon cancer.","authors":"Yiting Geng, Wei Xia, Xiao Zheng, Lujun Chen, You Zhou, Jun Feng, Ye Yuan, Mingyue Zhang, Jianwen Lu, Shanshan Wei, Wenwei Hu","doi":"10.1007/s10495-024-01986-x","DOIUrl":"10.1007/s10495-024-01986-x","url":null,"abstract":"<p><strong>Background: </strong>Cetuximab is extensively used in the treatment of metastatic colorectal cancer (mCRC). However, resistance poses a significant challenge to successful therapy. Recently, paraptosis, a non-classical programmed cell death, has garnered increased attention for its potential application value in antitumor treatments. We aimed to identify the essential pathways and signaling molecules involved in paraptosis inhibition and select them as therapeutic targets in cetuximab resistance. Additionally, engineered exosome technology is used as a drug delivery system with both targeted and effector properties.</p><p><strong>Results: </strong>By comparing the differential expression of paraptosis-related genes between drug-resistant colon cancer cells and sensitive cells, it was observed that the paraptosis level induced by cetuximab was significantly downregulated in drug-resistant cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified the focal adhesion kinase (FAK) signaling pathway as a key pathway involved in the suppression of paraptosis. The biological function of FAK in cetuximab-resistant cells was investigated through cell morphology observation, CCK-8 assay, colony formation assay, RT-qPCR, Western Blot, and loss-of-function experiments. The results showed that the FAK signaling pathway was significantly upregulated in cetuximab-resistant colon cancer cells, and siRNA interference targeting FAK could notably inhibit cell proliferation while upregulating the paraptosis level. Based on this, engineered colon cancer cells targeted and FAK siRNA loaded exosomes (CT-Exo-siFAK1) were constructed. In vitro experiments, CT-Exo-siFAK1 could effectively activate paraptosis and inhibit the proliferation of drug-resistant colon cancer cells. In vivo experiments also confirmed that CT-Exo-siFAK1 significantly suppressed tumor growth and metastasis while upregulating the paraptosis level.</p><p><strong>Conclusion: </strong>This study suggests that FAK signaling pathway-mediated inhibition of paraptosis levels is crucial in the sensitivity of cetuximab targeted therapy in colon cancer, and the use of engineered exosomes to deliver FAK siRNA may be an effective strategy to reverse cetuximab resistance.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496877","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":"Elevated serum mtDNA in COVID-19 patients is linked to SARS-CoV-2 envelope protein targeting mitochondrial VDAC1, inducing apoptosis and mtDNA release.","authors":"Anna Shteinfer-Kuzmine, Ankit Verma, Rut Bornshten, Eli Ben Chetrit, Ami Ben-Ya'acov, Hadas Pahima, Ethan Rubin, Yosef Mograbi, Eyal Shteyer, Varda Shoshan-Barmatz","doi":"10.1007/s10495-024-02025-5","DOIUrl":"10.1007/s10495-024-02025-5","url":null,"abstract":"<p><p>Mitochondria dysfunction is implicated in cell death, inflammation, and autoimmunity. During viral infections, some viruses employ different strategies to disrupt mitochondria-dependent apoptosis, while others, including SARS-CoV-2, induce host cell apoptosis to facilitate replication and immune system modulation. Given mitochondrial DNAs (mtDNA) role as a pro-inflammatory damage-associated molecular pattern in inflammatory diseases, we examined its levels in the serum of COVID-19 patients and found it to be high relative to levels in healthy donors. Furthermore, comparison of serum protein profiles between healthy individuals and SARS-CoV-2-infected patients revealed unique bands in the COVID-19 patients. Using mass spectroscopy, we identified over 15 proteins, whose levels in the serum of COVID-19 patients were 4- to 780-fold higher. As mtDNA release from the mitochondria is mediated by the oligomeric form of the mitochondrial-gatekeeper-the voltage-dependent anion-selective channel 1 (VDAC1)-we investigated whether SARS-CoV-2 protein alters VDAC1 expression. Among the three selected SARS-CoV-2 proteins, small envelope (E), nucleocapsid (N), and accessory 3b proteins, the E-protein induced VDAC1 overexpression, VDAC1 oligomerization, cell death, and mtDNA release. Additionally, this protein led to mitochondrial dysfunction, as evidenced by increased mitochondrial ROS production and cytosolic Ca²⁺ levels. These findings suggest that SARS-CoV-2 E-protein induces mitochondrial dysfunction, apoptosis, and mtDNA release via VDAC1 modulation. mtDNA that accumulates in the blood activates the cGAS-STING pathway, triggering inflammatory cytokine and chemokine expression that contribute to the cytokine storm and tissue damage seen in cases of severe COVID-19.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387462","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":"Heme oxygenase-1 binds gasdermin D to inhibit airway epithelium pyroptosis in allergic asthma.","authors":"Jiajia Lv, Min Wu, Zhenwei Xia","doi":"10.1007/s10495-024-02016-6","DOIUrl":"10.1007/s10495-024-02016-6","url":null,"abstract":"<p><p>This study explores how heme oxygenase-1 affects allergic airway inflammation, specifically focusing on airway epithelium pyroptosis. Findings suggest heme oxygenase-1 binds gasdermin D C-terminal to limit release of N-terminal, which affects NLRP3-caspase 1-gasdermin D trimer formation. This enhances comprehension of anti-inflammatory activity of heme oxygenase-1 in allergic disorders.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071805","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":"Disulfidptosis-related long non-coding RNA signature predicts the prognosis, tumor microenvironment, immunotherapy, and antitumor drug options in colon adenocarcinoma.","authors":"Kang Wang, Jing Yu, Qihuan Xu, Yuanhong Peng, Haibin Li, Yan Lu, Manzhao Ouyang","doi":"10.1007/s10495-024-02011-x","DOIUrl":"10.1007/s10495-024-02011-x","url":null,"abstract":"<p><p>This study aims to investigate the role and prognostic significance of long non-coding RNAs (lncRNAs) associated with disulfidptosis in colon adenocarcinoma (COAD). The TCGA database's clinical data and transcriptome profiles were employed. Analysis of previous studies identified 10 disulfidptosis-related genes (DRGs). We used these genes to construct a signature that could independently and accurately predict the prognosis of patients with COAD. The Kaplan-Meier (K-M) curve analysis showed that the lower-risk group had a better prognosis. With the help of multivariate Cox regression analysis, the risk score produced from the patient's signature might independently predict the outcomes. Utilizing a nomogram, the receiver operating characteristic (ROC) curve, and principal component analysis (PCA), the signature's predictive ability was also confirmed. It's interesting to note that immunotherapy, especially PD-1 immune checkpoint suppression, was more likely to benefit low-risk patients. The IC50 levels for certain anticancer agents were lower in the high-risk group. Finally, qRT-PCR analyses in colon cancer cell lines revealed elevated levels of lncRNAs CASC9, ZEB1-AS1, ATP2A1-AS1, SNHG7, AL683813.1, and AP003555.1, and reduced levels of FAM160A1-DT and AC112220.2, compared to normal cell lines. This signature offers insights into prognosis, tumor microenvironment, and options for immunotherapy and antitumor drugs in patients with COAD.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900754","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}