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












  • Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97.

    abstract::The cellular mechanisms that control protein degradation may constitute a non-oncogenic cancer cell vulnerability and, therefore, a therapeutic target. Although this proposition is supported by the clinical success of proteasome inhibitors in some malignancies, most cancers are resistant to proteasome inhibition. The ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Parzych K,Chinn TM,Chen Z,Loaiza S,Porsch F,Valbuena GN,Kleijnen MF,Karadimitris A,Gentleman E,Keun HC,Auner HW

    更新日期:2015-12-31 00:00:00

  • PKC signaling prevents irradiation-induced apoptosis of primary human fibroblasts.

    abstract::Primary cells respond to irradiation by activation of the DNA damage response and cell cycle arrest, which eventually leads to senescence or apoptosis. It is not clear in detail which signaling pathways or networks regulate the induction of either apoptosis or senescence. Primary human fibroblasts are able to withstan...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Bluwstein A,Kumar N,Léger K,Traenkle J,Oostrum Jv,Rehrauer H,Baudis M,Hottiger MO

    更新日期:2013-02-14 00:00:00

  • Consequences of blunting the mevalonate pathway in cancer identified by a pluri-omics approach.

    abstract::We have previously shown that the combination of statins and taxanes was a powerful trigger of HGT-1 human gastric cancer cells' apoptosis1. Importantly, several genes involved in the "Central carbon metabolism pathway in cancer", as reported in the Kyoto Encyclopedia of Genes and Genomes, were either up- (ACLY, ERBB2...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Goulitquer S,Croyal M,Lalande J,Royer AL,Guitton Y,Arzur D,Durand S,Le Jossic-Corcos C,Bouchereau A,Potin P,Akoka S,Antignac JP,Krempf M,Ferchaud-Roucher V,Giraudeau P,Corcos L

    更新日期:2018-07-03 00:00:00

  • LINC00675 activates androgen receptor axis signaling pathway to promote castration-resistant prostate cancer progression.

    abstract::The development of prostate cancer (PCa) from androgen-deprivation therapy (ADT) sensitive to castration resistant (CRPC) seriously impacts life quality and survival of PCa patients. Emerging evidence shows that long noncoding RNAs (lncRNAs) play vital roles in cancer initiation and progression. However, the inherited...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Yao M,Shi X,Li Y,Xiao Y,Butler W,Huang Y,Du L,Wu T,Bian X,Shi G,Ye D,Fu G,Wang J,Ren S

    更新日期:2020-08-15 00:00:00

  • High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling.

    abstract::Aldehyde dehydrogenase 1A1 (ALDH1A1) is one of cancer stem cell (CSC) markers, and high ALDH1 expression has been related to drug resistance and facilitated tumor growth. In this study, we investigated the potential involvement of nuclear factor erythroid 2-like 2 (NFE2L2/NRF2) in CSC-like properties of ALDH-high ovar...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Kim D,Choi BH,Ryoo IG,Kwak MK

    更新日期:2018-08-30 00:00:00

  • Conservation and divergence of mitochondrial apoptosis pathway in the Pacific oyster, Crassostrea gigas.

    abstract::Apoptosis is considered a crucial part of the host defense system in oysters according to previous reports; however, the exact process by which this occurs remains unclear. Besides, mitochondrial apoptosis is the primary method of apoptosis in vertebrate cells, but has been poorly studied in invertebrates and is quite...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Li Y,Zhang L,Qu T,Tang X,Li L,Zhang G

    更新日期:2017-07-06 00:00:00

  • Long non-coding RNA C2dat1 regulates CaMKIIδ expression to promote neuronal survival through the NF-κB signaling pathway following cerebral ischemia.

    abstract::Increasing evidence has demonstrated a significant role of long non-coding RNAs (lncRNAs) in diverse biological processes. However, their functions in cerebral ischemia remain largely unknown. Through an lncRNA array analysis in a rat model of focal cerebral ischemia/reperfusion (I/R), we have identified CAMK2D-associ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Xu Q,Deng F,Xing Z,Wu Z,Cen B,Xu S,Zhao Z,Nepomuceno R,Bhuiyan MI,Sun D,Wang QJ,Ji A

    更新日期:2016-03-31 00:00:00

  • The NF-κB1 is a key regulator of acute but not chronic renal injury.

    abstract::The NF-κB family of transcription factors is important for many cellular functions, in particular initiation and propagation of inflammatory and immune responses. However, recent data has suggested that different subunits of the NF-κB family can suppress the inflammatory response. NF-κB1, from the locus nfκb1, can inh...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Fearn A,Situmorang GR,Fox C,Oakley F,Howarth R,Wilson CL,Kiosia A,Robson MG,Mann DA,Moles A,Sheerin NS

    更新日期:2017-06-15 00:00:00

  • Hyperosmotic stress enhances cytotoxicity of SMAC mimetics.

    abstract::Inhibitors of apoptosis (IAP) proteins contribute to cell death resistance in malignancies and emerged as promising targets in cancer therapy. Currently, small molecules mimicking the IAP-antagonizing activity of endogenous second mitochondria-derived activator of caspases (SMAC) are evaluated in phase 1/2 clinical tr...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Bittner S,Knoll G,Ehrenschwender M

    更新日期:2017-08-03 00:00:00

  • Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis.

    abstract::Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppress...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Carlisi D,Buttitta G,Di Fiore R,Scerri C,Drago-Ferrante R,Vento R,Tesoriere G

    更新日期:2016-04-14 00:00:00

  • The interaction of interleukin-8 and PTEN inactivation promotes the malignant progression of head and neck squamous cell carcinoma via the STAT3 pathway.

    abstract::Interleukin-8 (IL-8) expression correlates with poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism is poorly understood. In this study, we found that overexpression of IL-8 correlated with poor outcome in HNSCC patients. IL-8 significantly increased ce...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Xu Q,Ma H,Chang H,Feng Z,Zhang C,Yang X

    更新日期:2020-05-29 00:00:00

  • Ganetespib synergizes with cyclophosphamide to improve survival of mice with autochthonous tumors in a mutant p53-dependent manner.

    abstract::The DNA-alkylating cytotoxic agent cyclophosphamide (CTX) is commonly used in the clinic to treat hematological malignancies like lymphomas and leukemias as well as solid tumors, but shows dose-dependent potentially life-threatening toxicities and can induce secondary malignancies. Thus, the clinical utility of CTX wo...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Alexandrova EM,Xu S,Moll UM

    更新日期:2017-03-16 00:00:00

  • Antagonizing circRNA_002581-miR-122-CPEB1 axis alleviates NASH through restoring PTEN-AMPK-mTOR pathway regulated autophagy.

    abstract::Circular RNAs (circRNAs) have been shown to play critical roles in cancer biology, but their functions in nonalcoholic steatohepatitis (NASH) remain unexplored. Full length of circRNA_002581 was amplified and sequenced, followed by RNA immunoprecipitation, RNA-Fluorescence in Situ Hybridization and dual luciferase rep...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Jin X,Gao J,Zheng R,Yu M,Ren Y,Yan T,Huang Y,Li Y

    更新日期:2020-02-13 00:00:00

  • Rac1 conditional deletion attenuates retinal ganglion cell apoptosis by accelerating autophagic flux in a mouse model of chronic ocular hypertension.

    abstract::Autophagy has a fundamental role in maintaining cell homeostasis. Although autophagy has been implicated in glaucomatous pathology, how it regulates retinal ganglion cell (RGC) injury is largely unknown. In the present work, we found that biphasic autophagy in RGCs occurred in a mouse model of chronic ocular hypertens...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhang ML,Zhao GL,Hou Y,Zhong SM,Xu LJ,Li F,Niu WR,Yuan F,Yang XL,Wang Z,Miao Y

    更新日期:2020-09-10 00:00:00

  • CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes.

    abstract::CEMIP (for "Cell migration-inducing protein" also called KIAA1199 and Hybid for "Hyaluronan-binding protein") expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid ...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Deroyer C,Charlier E,Neuville S,Malaise O,Gillet P,Kurth W,Chariot A,Malaise M,de Seny D

    更新日期:2019-02-04 00:00:00

  • Expression of ETS1 in gastric epithelial cells positively regulate inflammatory response in Helicobacter pylori-associated gastritis.

    abstract::Gastric epithelial cells (GECs) provide the first point of contact of the host by Helicobacter pylori (H. pylori), and the interaction between H. pylori and GECs plays a critical role in H. pylori-associated diseases. Aberrant expression of transcription factors (TFs) contributes to the pathogenesis of inflammatory di...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Teng Y,Cang B,Mao F,Chen W,Cheng P,Peng L,Luo P,Lu D,You N,Zou Q,Zhuang Y

    更新日期:2020-07-01 00:00:00

  • A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries.

    abstract::Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impa...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Domínguez-García S,Geribaldi-Doldán N,Gómez-Oliva R,Ruiz FA,Carrascal L,Bolívar J,Verástegui C,Garcia-Alloza M,Macías-Sánchez AJ,Hernández-Galán R,Nunez-Abades P,Castro C

    更新日期:2020-04-22 00:00:00

  • Long non-coding RNA LRRC75A-AS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC.

    abstract::As a common female malignancy, triple-negative breast cancer (TNBC) is the most serious subtype in breast cancer (BC). BAALC binder of MAP3K1 and KLF4 (BAALC) is a common oncogene in acute myelocytic leukemia (AML). We sought to explore the role of BAALC in TNBC. In this study, BAALC was significantly upregulated in T...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Li S,Wu D,Jia H,Zhang Z

    更新日期:2020-08-18 00:00:00

  • circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma.

    abstract::Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124. AQP3 was upregulate...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Chen G,Shi Y,Liu M,Sun J

    更新日期:2018-02-07 00:00:00

  • MicroRNA-148a deficiency promotes hepatic lipid metabolism and hepatocarcinogenesis in mice.

    abstract::miRNAs are involved in many physiologic and disease processes by virtue of degrading specific mRNAs or inhibiting their translation. miR-148a has been implicated in the control of tumor growth and cholesterol and triglyceride homeostasis using in vitro or in vivo gene expression- and silencing-based approaches. Here m...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Cheng L,Zhu Y,Han H,Zhang Q,Cui K,Shen H,Zhang J,Yan J,Prochownik E,Li Y

    更新日期:2017-07-13 00:00:00

  • Metabolic and molecular insights into an essential role of nicotinamide phosphoribosyltransferase.

    abstract::Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of N...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Zhang LQ,Van Haandel L,Xiong M,Huang P,Heruth DP,Bi C,Gaedigk R,Jiang X,Li DY,Wyckoff G,Grigoryev DN,Gao L,Li L,Wu M,Leeder JS,Ye SQ

    更新日期:2017-03-23 00:00:00

  • Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis.

    abstract::Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host response to infection that leads to uncontrolled inflammatory response followed by immunosuppression. However, despite the high mortality rate, no specific treatment modality or drugs with high efficacy is available for sepsis to date....

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审


    authors: Cao C,Yu M,Chai Y

    更新日期:2019-10-14 00:00:00

  • Robust high-throughput kinetic analysis of apoptosis with real-time high-content live-cell imaging.

    abstract::Quantitative and kinetic analyses of apoptotic cell death are integral components of exploring cell biology, measuring cellular stress responses, and performing high-throughput genomic/RNAi/drug screens. Here, we present a detailed method that integrates robust kinetic real-time high-content imaging with Annexin V lab...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Gelles JD,Chipuk JE

    更新日期:2016-12-01 00:00:00

  • Molecular subtype-specific responses of colon cancer cells to the SMAC mimetic Birinapant.

    abstract::Colorectal cancer is a molecularly heterogeneous disease. Responses to genotoxic chemotherapy in the adjuvant or palliative setting vary greatly between patients, and colorectal cancer cells often resist chemotherapy by evading apoptosis. Antagonists of an inhibitor of apoptosis proteins (IAPs) can restore defective a...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Fichtner M,Bozkurt E,Salvucci M,McCann C,McAllister KA,Halang L,Düssmann H,Kinsella S,Crawford N,Sessler T,Longley DB,Prehn JHM

    更新日期:2020-11-30 00:00:00

  • Cancer-associated fibroblasts promote progression and gemcitabine resistance via the SDF-1/SATB-1 pathway in pancreatic cancer.

    abstract::Cancer-associated fibroblasts (CAFs), a dominant component of the pancreatic tumor microenvironment, are mainly considered as promotors of malignant progression, but the underlying molecular mechanism remains unclear. Here, we show that SDF-1 secreted by CAFs stimulates malignant progression and gemcitabine resistance...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wei L,Ye H,Li G,Lu Y,Zhou Q,Zheng S,Lin Q,Liu Y,Li Z,Chen R

    更新日期:2018-10-18 00:00:00

  • miR-425 deficiency promotes necroptosis and dopaminergic neurodegeneration in Parkinson's disease.

    abstract::A major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra, and the causative mechanism is thought to be the activation of programmed neuronal death. Necroptosis is a regulated process of cell death triggered by RIPK1. Although the pathophysiology of PD has been st...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Hu YB,Zhang YF,Wang H,Ren RJ,Cui HL,Huang WY,Cheng Q,Chen HZ,Wang G

    更新日期:2019-08-05 00:00:00

  • Raddeanin A suppresses breast cancer-associated osteolysis through inhibiting osteoclasts and breast cancer cells.

    abstract::Bone metastasis is a severe complication of advanced breast cancer, resulting in osteolysis and increased mortality in patients. Raddeanin A (RA), isolated from traditional Chinese herbs, is an oleanane-type triterpenoid saponin with anticancer potential. In this study, we investigated the effects of RA in breast canc...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Wang Q,Mo J,Zhao C,Huang K,Feng M,He W,Wang J,Chen S,Xie Z,Ma J,Fan S

    更新日期:2018-03-07 00:00:00

  • Neutral lipids as early biomarkers of cellular fate: the case of α-synuclein overexpression.

    abstract::α-synuclein (α-syn) accumulation and aggregation is a common pathological factor found in synucleinopathies, a group of neurodegenerative disorders that includes Parkinson´s disease (PD). It has been proposed that lipid dyshomeostasis is responsible for the occurrence of PD-related processes, however, the precise role...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Alza NP,Conde MA,Scodelaro-Bilbao PG,Salvador GA

    更新日期:2021-01-07 00:00:00

  • Tryptophan-kynurenine pathway attenuates β-catenin-dependent pro-parasitic role of STING-TICAM2-IRF3-IDO1 signalosome in Toxoplasma gondii infection.

    abstract::Recent studies have documented the diverse role of host immunity in infection by the protozoan parasite, Toxoplasma gondii. However, the contribution of the β-catenin pathway in this process has not been explored. Here, we show that AKT-mediated phosphorylated β-catenin supports T. gondii multiplication which is arres...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Majumdar T,Sharma S,Kumar M,Hussain MA,Chauhan N,Kalia I,Sahu AK,Rana VS,Bharti R,Haldar AK,Singh AP,Mazumder S

    更新日期:2019-02-15 00:00:00

  • Proton irradiation orchestrates macrophage reprogramming through NFκB signaling.

    abstract::Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This...

    journal_title:Cell death & disease

    pub_type: 杂志文章


    authors: Genard G,Wera AC,Huart C,Le Calve B,Penninckx S,Fattaccioli A,Tabarrant T,Demazy C,Ninane N,Heuskin AC,Lucas S,Michiels C

    更新日期:2018-06-27 00:00:00