Apoptosis最新文献

{"title":"Targeting BACH1 by HPPE inhibits the Wnt/β-catenin pathway and malignant phenotype in glioblastoma cells.","authors":"Yuzhu Wang, Changxiao Yang, Li Guo, Peiyu Nie, Xiaowei Hu, Hongfeng Zhou, Huibo Li, Haiquan Tao, Jin Wu","doi":"10.1007/s10495-025-02183-0","DOIUrl":"https://doi.org/10.1007/s10495-025-02183-0","url":null,"abstract":"<p><p>BTB domain and CNC homology 1 (BACH1) has been reported to be a vital regulator of tumor progression. However, methods for targeting BACH1 in cancers have not been fully researched. In this study, we identified BACH1 as a poor prognosis-related factor in patients with GBM. Furthermore, a small-molecule compound, HPPE, was found to interact with BACH1 and inhibit the progression of GBM in vitro and in vivo. Molecular dynamics analysis, molecular docking simulation, MST assay, and co-IP experiments revealed that HPPE principally binds to BACH1 at the bZIP domain on the C-terminus and promotes the competitive binding of BACH1 and TCF-4, thus inhibiting formation of the β-catenin/TCF-4 complex. HPPE incubation inhibited proliferation, promoted apoptosis, and induced G2/M arrest, indicating a potential synergistic effect with temozolomide in GBM cells. RNA-seq, qRT‒PCR, and gene enrichment analyses revealed that the induction of HPPE repressed the Wnt/β-catenin pathway. Further experiments revealed that BTB domain deletion from BACH1 eliminated its ability to interact with TCF-4 and significantly rescued the inhibition of Wnt/β-catenin signaling and the reduction of malignant phenotype induced by HPPE in GBM cells. In vivo experiments revealed that HPPE prolonged the survival time of mice, inhibited Wnt/β-catenin pathway activity and had a synergistic effect with TMZ in a xenograft model. In summary, these findings provide potential combined therapeutic strategies for glioma by targeting the C-terminus of BACH1 and inhibiting the activation of WNT signaling.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068906","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":"High-dose tamoxifen impairs the homeostasis of the intestinal stem cell niche by enhancing fatty acid degradation and damaging mitochondria","authors":"Lu Xu,&nbsp;Xiangjun Liu,&nbsp;Jianhua Feng,&nbsp;Ke Wang,&nbsp;Xi Wang,&nbsp;Yujun Huang,&nbsp;Shubin Wang,&nbsp;Xudan Lei,&nbsp;Lingxiao Huang,&nbsp;Zhenni Xu,&nbsp;Jinyi Lang,&nbsp;Dengqun Liu","doi":"10.1007/s10495-025-02153-6","DOIUrl":"10.1007/s10495-025-02153-6","url":null,"abstract":"<div><p>Tamoxifen is therapeutically employed for breast and ovarian cancers, and it is also widely utilized to activate Cre recombinase in transgenic mice containing Cre-ERT locus. However, high dose tamoxifen (HDTAM) has been reported to induce many side effects in several organs and tissues. Intestinal stem cells (ISCs) play pivotal roles in sustaining the epithelial homeostasis and intestinal functionality. In this study, we systematically investigated the influences of HDTAM on ISCs and their niche. It was found that HDTAM treatment decreased the body weight and the length of small intestines (SI), damaged the gross and histological morphology of SI. Notably, HDTAM dramatically inhibited the proliferation, differentiation, gene expression of ISCs in vivo and in vitro. RNA-Seq results demonstrated that these changes caused by HDTAM were significantly correlated with the degradation of intestinal fatty acids and the process of fatty acid oxidation. Mechanistically, HDTAM impaired the morphology and function of mitochondria of intestinal epithelial cells, increased the endoplasmic reticulum (ER) contents in Paneth cells. Therefore, we concluded that HDTAM could result in a disruption for the function and homeostasis of ISCs, and the interruption of fatty acid utilization might be responsible for these effects. This study implicates a careful use and evaluation of tamoxifen is in necessity when it’s used for intestinal research.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"30 9-10","pages":"2421 - 2434"},"PeriodicalIF":8.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068940","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":"RIPK1-targeted therapy alleviates intervertebral disc degeneration via inhibiting nucleus pulposus PANoptosis.","authors":"Zhenyu Zhu, Fanqi Kong, Feng Jiang, Jialin Jiang, Danni Quan, Jiazheng Guo, Kaiqiang Sun, Jiangang Shi, Changnan Wang, Chunlin Zhuang, Ximing Xu","doi":"10.1007/s10495-025-02169-y","DOIUrl":"https://doi.org/10.1007/s10495-025-02169-y","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) is a major contributor to lumbar diseases, including low back pain, herniation, and stenosis. Despite significant efforts, there have been limited improvements in treatments to alleviate IVDD. The nucleus pulposus (NP) is a crucial component of the intervertebral disc (IVD), responsible for secreting aggrecan, collagen II, and other extracellular matrix components. Programmed cell death (PCD) of NP cells is believed to play a central role in IVDD. RIPK1 is a key mediator of PCD and recently reported PANoptosis, playing essential role in kidney injury, arteriosclerosis, and acute or chronic inflammation-related diseases. We collected varied degenerated human IVD specimens to examine the expression of RIPK1 and downstream cell death-related markers, including GSDMD, Caspase3, and MLKL, which are indicative of pyroptosis, apoptosis, necroptosis, or the recently denominated PANoptosis. In vitro, we performed RIPK1 knockdown and overexpression to study their effects on IVDD. in vivo, we constructed RIPK1 conditional knockout (CKO) mice to confirm the role of RIPK1 in IVDD. We also utilized a small molecule targeted inhibitor to explore its effects on IVDD in vitro and in vivo. Phosphorylated RIPK1 (p-RIPK1) was significantly increased during IVDD in both human and mouse models. Knockout of RIPK1 effectively alleviated IVDD, as evidenced by the RIPK1 cko mice. Further pathological staining and western blot analysis revealed the overexpression of GSDMD, Caspase3, and MLKL, indicating that RIPK1-mediated PANoptosis plays a crucial role in IVDD. in vitro, overexpression of RIPK1 in NP cells exacerbated PANoptosis and degeneration, while RIPK1 knockdown inhibited these processes. We developed a RIPK1-targeted small molecular inhibitor, compound 3-47, which demonstrated superior efficacy in inhibiting p-RIPK1. Both in vitro and in vivo, 3-47 showed remarkable effects in alleviating IVDD by inhibiting RIPK1-mediated PANoptosis. RIPK1-mediated PANoptosis of NP cells plays a critical role in IVDD. The molecular inhibitor 3-47 could effectively delay IVDD progression in mice, highlighting its therapeutic potential.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068913","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":"Mechanistic study on the role of multi-pathway autophagy in ovarian aging: literature review.","authors":"Xinyu Zhu, Huihui Li, Tingting Xue, Shu Wang, Ruixiang Zhu, Jiali Luo, Ruotong Ju, Puhua Zhang, Xiangrong Cui, Xuan Jing","doi":"10.1007/s10495-025-02181-2","DOIUrl":"https://doi.org/10.1007/s10495-025-02181-2","url":null,"abstract":"<p><p>Ovarian aging is one of the common diseases in the female reproductive system. It is characterized by complex etiologies, involving multiple factors such as genetics, environment, metabolism, and cellular stress. In recent years, autophagy, a crucial cellular self-degradation and repair mechanism, has received substantial attention for its role in maintaining and deteriorating ovarian function. This review systematically summarizes the molecular mechanisms of autophagy and its regulation, as well as the latest research progress of macroautophagy, chaperone-mediated autophagy (CMA) and mitophagy in ovarian aging. Studies have shown that dysregulation of autophagic pathways is closely associated with decreased oocyte quality and reduced ovarian reserve function. Additionally, signaling pathways such as PI3K, AMPK, and mTOR participate in the process of ovarian aging by regulating autophagic activity. Although numerous studies have revealed the critical role of autophagy in ovarian aging, many issues remain to be resolved, such as the crosstalk mechanisms between different autophagic pathways and the precise spatiotemporal dynamics of the autophagic regulatory network. A deep understanding of the regulatory network of multi-pathway autophagy will provide new insights for developing intervention strategies to delay ovarian aging, holding significant scientific and clinical application value.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068949","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":"Mitophagy: a novel avenue for herbal medicines alleviating myocardial ischemia/reperfusion injury.","authors":"Mengqi Liao, Ling Men, Ming Gong, Yuanyuan Li, Yan Wang, Desheng Xu, Jienan Luan, Hua Zhou, Mengnan Liu, Mingtai Chen","doi":"10.1007/s10495-025-02178-x","DOIUrl":"https://doi.org/10.1007/s10495-025-02178-x","url":null,"abstract":"<p><p>Myocardial ischemia-reperfusion injury (MIRI) has a high incidence and is difficult to cure. Studies have shown that mitophagy is the key mechanism. This review systematically summarizes all documented herbal preparations and bioactive monomers targeting mitophagy for MIRI treatment, which may serve as a valuable reference for future research on herbal medicine-mediated mitophagy regulation. We conducted comprehensive literature searches in PubMed, Embase, Web of Science, and CNKI databases using the keywords \"cardiovascular diseases,\" \"mitophagy,\" \"myocardial ischemia-reperfusion injury,\" \"herbal medicine,\" \"mechanism,\" and \"therapeutic\" for studies published within the last five years up to July 2025. Studies on herbal medicine interventions unrelated to mitophagy were excluded. Our analysis reveals that mitophagy plays a crucial role in attenuating the detrimental effects of MIRI. Furthermore, herbal medicine demonstrates therapeutic efficacy in maintaining homeostatic balance of mitophagy during MIRI. Herbal medicines can precisely regulate mitophagy via the PTEN-induced putative kinase 1 (PINK1)-parkin pathway, and modulate the expression of BCL2 interacting protein 3 (BNIP3), FUN14 domain-containing protein 1 (FUNDC1), NIP3-like protein X (NIX). Herbal medicines exert protective effects against MIRI through diverse mechanisms and signaling pathways by targeting mitophagy. While mitophagy represents a promising frontier for future cardiovascular research, current herbal medicine applications remain predominantly confined to animal and cellular models, with only limited clinical translation. The findings presented herein are anticipated to provide clinicians and cardiovascular researchers with valuable therapeutic strategies and novel research directions.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038954","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":"Harnessing cuproptosis: a new avenue for targeted cancer therapies.","authors":"Anil Dharavath, Sivkan Kaur, P V Drupad Mohan, Santosh Kumar Guru","doi":"10.1007/s10495-025-02174-1","DOIUrl":"https://doi.org/10.1007/s10495-025-02174-1","url":null,"abstract":"<p><p>Copper-induced cell death, referred to as cuproptosis, introduces a new approach for cancer treatment by utilizing the toxic effects of copper. While copper is vital for enzymatic processes, it becomes harmful at excessive concentrations. Cuproptosis is characterized by mitochondrial impairment resulting from copper interacting with lipoylated components of the tricarboxylic acid (TCA) cycle, leading to proteotoxic stress and targeted cell death. This mechanism is distinct from traditional apoptosis and necrosis. Disruption of copper balance and associated genes, such as FDX1, LIAS, and DLAT, has been linked to various types of cancer. In this review, we outline the timeline of cuproptosis discovery and its comparison with other cell death mechanisms. In addition, we discuss copper homeostasis and copper metabolism in normal human physiology. We also reviewed how the disruption of copper balance can lead to cuproptosis and its involvement in tumorigenesis. Furthermore, we provided an overview of the various genes associated with cuproptosis and their roles in cancer. Given the numerous targets identified, we also provide a thorough overview of the drugs linked to cuproptosis and discuss their clinical relevance and prospects. This review indicates that targeting cuproptosis may serve as a novel therapeutic approach for cancer treatment.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039012","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":"Oxidative stress and ferroptosis in diabetic cardiomyopathy: mechanistic interplay and therapeutic implications.","authors":"Shan Li, Yuhe Shu, Shuyu Yang, Simin Zhang, Haoling Chen, Dan Wu, Bo Li, Li Dong","doi":"10.1007/s10495-025-02170-5","DOIUrl":"https://doi.org/10.1007/s10495-025-02170-5","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a severe cardiovascular complication of diabetes mellitus, characterized by pathological changes such as cardiomyocyte hypertrophy, necrosis, and myocardial fibrosis, which can ultimately lead to heart failure. However, its underlying mechanisms remain incompletely understood, limiting the development of effective therapeutic approaches. In recent years, the critical roles of oxidative stress and ferroptosis in the pathogenesis of DCM have attracted increasing attention. Oxidative stress is a state where the imbalance between oxidative and antioxidant systems results in excessive production of reactive oxygen species (ROS), thereby damaging key cellular structures such as cardiomyocyte membranes and mitochondria, and promoting the occurrence and development of DCM. Ferroptosis is an iron-dependent form of regulated cell death, which has been confirmed to be involved in the injury and death of diabetic cardiomyocytes.This article reviews the interaction between oxidative stress and ferroptosis in DCM as well as their molecular mechanisms, explores their complex relationship in the occurrence and progression of the disease, and proposes potential therapeutic strategies based on this mechanistic framework. It aims to provide researchers and clinicians with a comprehensive and up-to-date reference to collectively advance the prevention and treatment of DCM.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022783","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":"Cathayanon E induces apoptosis and enhances oxaliplatin sensitivity in colorectal cancer through suppression of MCL1.","authors":"Liang Cen, Xin Hu, Guozhen An, Lichao Wang, Yanghao Hu, Junjie He, Hanghang Qin, Yongsen Li, Hongjuan Cui","doi":"10.1007/s10495-025-02167-0","DOIUrl":"https://doi.org/10.1007/s10495-025-02167-0","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common and lethal malignancies worldwide, with treatment failure often attributed to chemoresistance and evasion of apoptosis. Cathayanon E (CE), a natural chalcone derivative isolated from Morus alba, has shown anticancer potential, but its role and mechanism in CRC remain largely unexplored. In this study, CE significantly inhibited CRC cell proliferation and induced apoptosis both in vitro and in vivo. Mechanistically, CE directly bound to the anti-apoptotic protein MCL1 and promoted its β-TRCP-mediated ubiquitination and proteasomal degradation, thereby inducing mitochondrial apoptotic signaling. Overexpression of MCL1 reversed the antiproliferative and pro-apoptotic effects of CE, validating MCL1 as a functional target of CE. Furthermore, CE markedly enhanced the chemosensitivity of CRC cells to oxaliplatin, resulting in synergistic tumor suppression in xenograft models. These findings highlight CE as a promising natural agent that targets MCL1 to overcome chemoresistance and improve therapeutic outcomes in colorectal cancer.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022781","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":"HMGB1: a multifaceted mediator of cell death pathways in cardiovascular diseases.","authors":"Yue Shi, Yixuan Ma, Rong Wang, Xiaoer Liu, Wenqing Duan, Dejian Huang, Xiaoting Wang, Jinming Zhao, Rubin Tan","doi":"10.1007/s10495-025-02144-7","DOIUrl":"https://doi.org/10.1007/s10495-025-02144-7","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are a leading cause of death globally, responsible for 32% of all fatalities. They significantly reduce quality of life and life expectancy, while imposing a substantial economic burden on healthcare systems in different countries. High mobility group box 1 (HMGB1), a location-dependent multifunctional protein, plays a significant role in various cell death pathways associated with CVDs. While its release at the early stages of disease may stimulate immune and inflammatory responses, aiding microbial clearance and wound healing, the accumulation of HMGB1 with disease progression disrupts the balance between autophagy and apoptosis. Excessive intracellular and extracellular HMGB1 is implicated in diverse forms of cell death, including PANoptosis, ferroptosis, and efferocytosis, highlighting its complex role in maintaining cellular homeostasis and responding to injury. Understanding the intricate regulatory functions of HMGB1 in these processes is critical for developing targeted therapeutic strategies to address cardiovascular pathologies. Preclinical studies have demonstrated the therapeutic potential of targeting HMGB1 release and expression in various CVD models, establishing it as an attractive therapeutic target. Future research focusing on combined strategies that integrate HMGB1 with other targets holds promise for advancing CVD treatment.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022779","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":"Metabolic cell death in cancer: mechanisms and therapeutic potential.","authors":"Yujinpeng Hao, Jun Shao, Naqi Lian, Mianli Bian","doi":"10.1007/s10495-025-02176-z","DOIUrl":"https://doi.org/10.1007/s10495-025-02176-z","url":null,"abstract":"<p><p>A defining hallmark of malignant tumours lies in their pronounced resistance to programmed cell death mechanisms. This intrinsic resilience enables cancer cells to circumvent physiological clearance, thereby sustaining unchecked proliferation and survival. Emerging research has revealed that metabolic dysregulation can precipitate a distinctive form of programmed cell death, termed metabolism-linked regulated cell death (RCD), establishing it as a novel paradigm of cellular self-elimination. This systematic review provides an in-depth analysis of the molecular mechanisms orchestrating various metabolic cell death modalities, including pyroptosis, immunogenic cell death (ICD), necroptosis, ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, alkaliptosis, and methuosis. Furthermore, it critically evaluates their therapeutic potential in oncology. By elucidating the intricate interplay among these signalling cascades, this review describes innovative precision medicine strategies that harness metabolism-driven cell death for targeted cancer interventions.</p>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022795","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}