Procaspase-3-activating compound 1 stabilizes hypoxia-inducible factor 1α and induces DNA damage by sequestering ferrous iron.


:Procaspase-3-activating compound 1 (PAC-1) induces procaspase-3 activation via zinc chelation. However, whether PAC-1 employs other mechanisms remains unknown. Here we systematically screened for potent PAC-1 targets using 29 enhanced green fluorescent protein-labeled reporter cell lines and identified hypoxia-inducible factor 1α (HIF1α) and RAD51 pathways as PAC-1 targets. These results were verified in HepG2 cells and two other cancer cell lines. Mechanistically, PAC-1 specifically blocked HIF1α hydroxylation and upregulated HIF1α target genes. In addition, DNA damage, G1/S cell cycle arrest, and the inhibition of DNA synthesis were induced following PAC-1 administration. Interestingly, by using ferrozine-iron sequestration and iron titration assays, we uncovered the iron sequestering capacity of PAC-1. Additionally, the expression levels of iron shortage-related genes were also increased in PAC-1-treated cells, and iron (II) supplementation reversed all of the observed cellular responses. Thus, our results indicate that PAC-1 induces HIF1α stabilization and DNA damage by sequestering ferrous iron.


Cell Death Dis


Cell death & disease


Li F,Wei A,Bu L,Long L,Chen W,Wang C,Zhao C,Wang L




Has Abstract


2018-10-04 00:00:00












  • Cell density-dependent proteolysis by HtrA1 induces translocation of zyxin to the nucleus and increased cell survival.

    abstract::Proteases modulate critical processes in cutaneous tissue repair to orchestrate inflammation, cell proliferation and tissue remodeling. However, the functional consequences and implications in healing impairments of most cleavage events are not understood. Using iTRAQ-based Terminal Amine Isotopic Labeling of Substrat...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Sabino F,Madzharova E,Auf dem Keller U

    更新日期:2020-08-21 00:00:00

  • Anti-bacterial and anti-viral nanchangmycin displays anti-myeloma activity by targeting Otub1 and c-Maf.

    abstract::As a deubiqutinase Otub1 stabilizes and promotes the oncogenic activity of the transcription factor c-Maf in multiple myeloma (MM), a malignancy of plasma cells. In the screen for bioactive inhibitors of the Otub1/c-Maf axis for MM treatment, nanchangmycin (Nam), a polyketide antibiotic, was identified to suppress c-M...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Xu Y,Sun T,Zeng K,Xu M,Chen J,Xu X,Zhang Z,Cao B,Tang X,Wu D,Kong Y,Zeng Y,Mao X

    更新日期:2020-09-30 00:00:00

  • Multiple mechanisms mediating carbon monoxide inhibition of the voltage-gated K+ channel Kv1.5.

    abstract::The voltage-gated K+ channel has key roles in the vasculature and in atrial excitability and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1....

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Al-Owais MM,Hettiarachchi NT,Boyle JP,Scragg JL,Elies J,Dallas ML,Lippiat JD,Steele DS,Peers C

    更新日期:2017-11-02 00:00:00

  • Bax retrotranslocation potentiates Bcl-xL's antiapoptotic activity and is essential for switch-like transitions between MOMP competency and resistance.

    abstract::The rapid, typically all-or-none process of mitochondrial outer membrane permeabilization (MOMP) constitutes a primary cell death decision that is controlled by the Bcl-2 family interactome. However, how strict all-or-none MOMP decisions are governed by and emanate from the dynamic interplay of pro- and antiapoptotic ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Hantusch A,Das KK,García-Sáez AJ,Brunner T,Rehm M

    更新日期:2018-04-01 00:00:00

  • Magmas functions as a ROS regulator and provides cytoprotection against oxidative stress-mediated damages.

    abstract::Redox imbalance generates multiple cellular damages leading to oxidative stress-mediated pathological conditions such as neurodegenerative diseases and cancer progression. Therefore, maintenance of reactive oxygen species (ROS) homeostasis is most important that involves well-defined antioxidant machinery. In the pres...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Srivastava S,Sinha D,Saha PP,Marthala H,D'Silva P

    更新日期:2014-08-28 00:00:00

  • Novel osmotin attenuates glutamate-induced synaptic dysfunction and neurodegeneration via the JNK/PI3K/Akt pathway in postnatal rat brain.

    abstract::The glutamate-induced excitotoxicity pathway has been reported in several neurodegenerative diseases. Molecules that inhibit the release of glutamate or cause the overactivation of glutamate receptors can minimize neuronal cell death in these diseases. Osmotin, a homolog of mammalian adiponectin, is a plant protein fr...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Shah SA,Lee HY,Bressan RA,Yun DJ,Kim MO

    更新日期:2014-01-30 00:00:00

  • Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis.

    abstract::In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival c...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Ruiz A,Rockfield S,Taran N,Haller E,Engelman RW,Flores I,Panina-Bordignon P,Nanjundan M

    更新日期:2016-01-14 00:00:00

  • Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis.

    abstract::Peroxiredoxin (Prdx) 2 is an antioxidant protein that utilizes its redox-sensitive cysteine groups to reduce hydrogen peroxide molecules and protect cells against oxidative damage from reactive oxygen species (ROS). However, its function in trophoblasts at the maternal-fetal interface has not been clarified yet. In th...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wu F,Tian F,Zeng W,Liu X,Fan J,Lin Y,Zhang Y

    更新日期:2017-06-29 00:00:00

  • DEPTOR is a direct p53 target that suppresses cell growth and chemosensitivity.

    abstract::DEP-domain containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, has essential roles in several processes, including cell growth, metabolism, apoptosis, and immunity. DEPTOR expression has been shown to be diversely controlled at transcriptional levels in cell- and context-specific manners. However, ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Cui D,Dai X,Gong L,Chen X,Wang L,Xiong X,Zhao Y

    更新日期:2020-11-12 00:00:00

  • Differential activity of GSK-3 isoforms regulates NF-κB and TRAIL- or TNFα induced apoptosis in pancreatic cancer cells.

    abstract::While TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell li...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhang JS,Herreros-Villanueva M,Koenig A,Deng Z,de Narvajas AA,Gomez TS,Meng X,Bujanda L,Ellenrieder V,Li XK,Kaufmann SH,Billadeau DD

    更新日期:2014-03-27 00:00:00

  • LncRNA UCA1 promotes tumor metastasis by inducing miR-203/ZEB2 axis in gastric cancer.

    abstract::Increasing studies showed that long-noncoding RNAs (lncRNAs) play important roles in the biological processes, including cancer initiation and progression. However, little is known about the exact role and regulation mechanism of lncRNA UCA1 during the progression of gastric cancer (GC). In this study, we found that U...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Gong P,Qiao F,Wu H,Cui H,Li Y,Zheng Y,Zhou M,Fan H

    更新日期:2018-11-21 00:00:00

  • Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma.

    abstract::It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The c...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wang H,Wu Q,Liu Z,Luo X,Fan Y,Liu Y,Zhang Y,Hua S,Fu Q,Zhao M,Chen Y,Fang W,Lv X

    更新日期:2014-04-10 00:00:00

  • Author Correction: Autophagic degradation of caveolin-1 promotes liver sinusoidal endothelial cells defenestration.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Cell death & disease

    pub_type: 已发布勘误


    authors: Luo X,Wang D,Zhu X,Wang G,You Y,Ning Z,Li Y,Jin S,Huang Y,Hu Y,Chen T,Meng Y,Li X

    更新日期:2019-06-17 00:00:00

  • Wnt3a mitigates acute lung injury by reducing P2X7 receptor-mediated alveolar epithelial type I cell death.

    abstract::Acute lung injury (ALI) is characterized by pulmonary endothelial and epithelial cell damage, and loss of the alveolar-capillary barrier. We have previously shown that P2X7 receptor (P2X7R), a cell death receptor, is specifically expressed in alveolar epithelial type I cells (AEC I). In this study, we hypothesized tha...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Guo Y,Mishra A,Weng T,Chintagari NR,Wang Y,Zhao C,Huang C,Liu L

    更新日期:2014-06-12 00:00:00

  • IFN-γ promoted exosomes from mesenchymal stem cells to attenuate colitis via miR-125a and miR-125b.

    abstract::Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Yang R,Huang H,Cui S,Zhou Y,Zhang T,Zhou Y

    更新日期:2020-07-30 00:00:00

  • Decreased expression of ARHGAP15 promotes the development of colorectal cancer through PTEN/AKT/FOXO1 axis.

    abstract::Copious evidence demonstrates the crucial role of Rho GTPase-activating proteins in human malignancies. The downregulation of Rho GTPase-activating protein 15 (ARHGAP15), a Rac1-specific GAP, has been observed in glioma and pancreatic ductal adenocarcinoma. The present study explored the expression in colorectal cance...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Pan S,Deng Y,Fu J,Zhang Y,Zhang Z,Ru X,Qin X

    更新日期:2018-06-04 00:00:00

  • MicroRNA-181a-5p and microRNA-181a-3p cooperatively restrict vascular inflammation and atherosclerosis.

    abstract::MicroRNAs have emerged as important post-transcriptional regulators of gene expression and are involved in diverse diseases and cellular process. Decreased expression of miR-181a has been observed in the patients with coronary artery disease, but its function and mechanism in atherogenesis is not clear. This study was...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Su Y,Yuan J,Zhang F,Lei Q,Zhang T,Li K,Guo J,Hong Y,Bu G,Lv X,Liang S,Ou J,Zhou J,Luo B,Shang J

    更新日期:2019-05-07 00:00:00

  • Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification.

    abstract::Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we conf...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Xu X,Yin Y,Tang J,Xie Y,Han Z,Zhang X,Liu Q,Qin X,Huang X,Sun B

    更新日期:2017-10-12 00:00:00

  • MicroRNA-34a: a potential therapeutic target in human cancer.

    abstract::MicroRNAs (miRs) are small noncoding RNAs that negatively regulate gene expression by binding to the three untranslated regions of their target mRNAs. Deregulations of miRs were shown to play pivotal roles in tumorigenesis and progression. Recent research efforts have been devoted to translating these basic discoverie...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审


    authors: Li XJ,Ren ZJ,Tang JH

    更新日期:2014-07-17 00:00:00

  • Inhibition of TXNIP expression in vivo blocks early pathologies of diabetic retinopathy.

    abstract::Evidence is mounting that proinflammatory and proapoptotic thioredoxin-interacting protein (TXNIP) has a causative role in the development of diabetes. However, there are no studies investigating the role of TXNIP in diabetic retinopathy (DR). Here, we show that, in diabetic rats, TXNIP expression and hexosamine biosy...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Perrone L,Devi TS,Hosoya KI,Terasaki T,Singh LP

    更新日期:2010-08-19 00:00:00

  • DJ-1 modulates the unfolded protein response and cell death via upregulation of ATF4 following ER stress.

    abstract::The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including PARK7 which encodes...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Yang J,Kim KS,Iyirhiaro GO,Marcogliese PC,Callaghan SM,Qu D,Kim WJ,Slack RS,Park DS

    更新日期:2019-02-12 00:00:00

  • microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway.

    abstract::The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target o...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhang Y,Wei Y,Li X,Liang X,Wang L,Song J,Zhang X,Zhang C,Niu J,Zhang P,Ren Z,Tang B

    更新日期:2018-01-26 00:00:00

  • Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling.

    abstract::BMP2 expression is spatiotemporally correlated with embryo implantation and is crucial for endometrial decidualization and fertility in mice. BMP2 has been reported to increase the mesenchymal adhesion molecule N-cadherin and enhance cell invasion in cancer cells; moreover, studies suggest that N-cadherin promotes pla...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhao HJ,Klausen C,Li Y,Zhu H,Wang YL,Leung PCK

    更新日期:2018-02-07 00:00:00

  • The thiosemicarbazone Me2NNMe2 induces paraptosis by disrupting the ER thiol redox homeostasis based on protein disulfide isomerase inhibition.

    abstract::Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Hager S,Korbula K,Bielec B,Grusch M,Pirker C,Schosserer M,Liendl L,Lang M,Grillari J,Nowikovsky K,Pape VFS,Mohr T,Szakács G,Keppler BK,Berger W,Kowol CR,Heffeter P

    更新日期:2018-10-15 00:00:00

  • Phosphorylation of cyclophilin D at serine 191 regulates mitochondrial permeability transition pore opening and cell death after ischemia-reperfusion.

    abstract::The mitochondrial permeability transition pore (mPTP) plays a critical role in the pathogenesis of cardiovascular diseases, including ischemia/reperfusion injury. Although the pore structure is still unresolved, the mechanism through which cyclophilin D (CypD) regulates mPTP opening is the subject of intensive studies...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Hurst S,Gonnot F,Dia M,Crola Da Silva C,Gomez L,Sheu SS

    更新日期:2020-08-19 00:00:00

  • Transcription factor Six2 mediates the protection of GDNF on 6-OHDA lesioned dopaminergic neurons by regulating Smurf1 expression.

    abstract::Glial cell line-derived neurotrophic factor (GDNF) has strong neuroprotective and neurorestorative effects on dopaminergic (DA) neurons in the substantia nigra (SN); however, the underlying molecular mechanisms remain to be fully elucidated. In this study, we found that the expression level of transcription factor Six...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Gao J,Kang XY,Sun S,Li L,Zhang BL,Li YQ,Gao DS

    更新日期:2016-05-05 00:00:00

  • miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice.

    abstract::This corrects the article DOI: 10.1038/cddis.2017.172. ...

    journal_title:Cell death & disease

    pub_type: 杂志文章,已发布勘误


    authors: Rodrigues PM,Afonso MB,Simão AL,Carvalho CC,Trindade A,Duarte A,Borralho PM,Machado MV,Cortez-Pinto H,Rodrigues CM,Castro RE

    更新日期:2017-05-25 00:00:00

  • GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.

    abstract::Glycogen synthase kinase-3β (GSK-3β) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: L'Episcopo F,Drouin-Ouellet J,Tirolo C,Pulvirenti A,Giugno R,Testa N,Caniglia S,Serapide MF,Cisbani G,Barker RA,Cicchetti F,Marchetti B

    更新日期:2016-04-28 00:00:00

  • Testes-specific protease 50 promotes cell invasion and metastasis by increasing NF-kappaB-dependent matrix metalloproteinase-9 expression.

    abstract::The high mortality in breast cancer is often associated with metastatic progression in patients. Previously we have demonstrated that testes-specific protease 50 (TSP50), an oncogene overexpressed in breast cancer samples, could promote cell proliferation and tumorigenesis. However, whether TSP50 also has a key role i...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Song ZB,Ni JS,Wu P,Bao YL,Liu T,Li M,Fan C,Zhang WJ,Sun LG,Huang YX,Li YX

    更新日期:2015-03-26 00:00:00

  • Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis.

    abstract::Reactive gliosis is an early pathological feature common to most neurodegenerative diseases, yet its regulation and impact remain poorly understood. Normally astrocytes maintain a critical homeostatic balance. After stress or injury they undergo rapid parainflammatory activation, characterized by hypertrophy, and incr...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Livne-Bar I,Lam S,Chan D,Guo X,Askar I,Nahirnyj A,Flanagan JG,Sivak JM

    更新日期:2016-09-29 00:00:00