Abstract:
:We previously reported that marchantin M (Mar) is an active agent to induce apoptosis in human prostate cancer (PCa), but the molecular mechanisms of action remain largely unknown. Here, we demonstrate that Mar potently inhibited chymotrypsin-like and peptidyl-glutamyl peptide-hydrolyzing activities of 20S proteasome both in in vitro and intracellular systems and significantly induced the accumulation of polyubiquitinated proteins in PCa cells. The computational modeling analysis suggested that Mar non-covalently bound to active sites of proteasome β5 and β1 subunits, resulting in a non-competitive inhibition. Proteasome inhibition by Mar subsequently resulted in endoplasmic reticulum (ER) stress, as evidenced by elevated glucose-regulated protein 78 and CHOP, increased phospho-eukaryotic translation initiation factor 2α (eIF(2α)), splicing of X-box-binding protein-1 and dilation of the ER. However, Mar-mediated cell death was not completely impaired by a pan inhibitor of caspases. Further studies revealed that the Mar-induced cell death was greatly associated with the activation of autophagy, as indicated by the significant induction of microtubule-associated protein-1 light chain-3 beta (LC3B) expression and conversion. Electron microscopic and green fluorescent protein-tagged LC3B analyses further demonstrated the ability of autophagy induction by Mar. Time kinetic studies revealed that Mar induced a rapid and highly sustained processing of LC3B in treated cells and simultaneously decreased the expression of p62/SQSTM1. Pharmacological blockade or knockdown of LC3B and Atg5 attenuated Mar-mediated cell death. The autophagic response triggered by Mar required the activation of RNA-dependent protein kinase-like ER kinase/eIF(2α) and suppression of the phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin axis via preventing activation and expression of Akt. Our results identified a novel mechanism for the cytotoxic effect of Mar, which strengthens it as a potential agent in cancer chemotherapy.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Jiang H,Sun J,Xu Q,Liu Y,Wei J,Young CY,Yuan H,Lou Hdoi
10.1038/cddis.2013.285subject
Has Abstractpub_date
2013-08-08 00:00:00pages
e761issn
2041-4889pii
cddis2013285journal_volume
4pub_type
杂志文章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
doi:10.1038/cddis.2017.355
更新日期:2017-08-03 00:00:00
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
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abstract::The homolog of p53 gene, p63, encodes multiple p63 protein isoforms. TAp63 proteins contain an N-terminal transactivation domain similar to that of p53 and function as tumor suppressors; whereas ΔNp63 isoforms, which lack the intact N-terminal transactivation domain, are associated with human tumorigenesis. Accumulati...
journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2013-12-05 00:00:00
abstract::Gastric cancer (GC) is one of the most frequent malignancies, and increasing evidence supports the contribution of microRNA (miRNAs) to cancer progression. miR-1254 has been confirmed to participate in the regulation of various cancers, while the function of miR-1254 in GC remains unknown. In this study, we investigat...
journal_title:Cell death & disease
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doi:10.1038/s41419-018-1262-x
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abstract::Direct pharmacological targeting of the anti-apoptotic B-cell lymphoma-2 (BCL-2) family is an attractive therapeutic strategy for treating cancer. Obatoclax is a pan-BCL-2 family inhibitor currently in clinical development. Here we show that, although obatoclax can induce mitochondrial apoptosis dependent on BCL-2 ass...
journal_title:Cell death & disease
pub_type: 杂志文章
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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
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abstract::Breast cancer is the most common cancer type in women. Long non-coding RNAs (lncRNAs) have been reported as potential new diagnostic markers, prognostic factors, and therapeutic targets in cancer. However, the specific roles and mechanisms of lncRNAs in breast cancer remain to be elucidated. Here we demonstrated the d...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Glycine decarboxylase (GLDC) belongs to the glycine cleavage system and is involved in one-carbon metabolism. We previously reported that GLDC downregulation enhances hepatocellular carcinoma (HCC) progression and intrahepatic metastasis through decreasing ROS-mediated ubiquitination of cofilin. The role of autophagy ...
journal_title:Cell death & disease
pub_type: 杂志文章
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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
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abstract::MicroRNAs (miRNAs) have been validated to play prominent roles in the occurrence and development of bladder cancer (BCa). MiR-22 was previously reported to act as a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in BCa remain unclear. Here, we find t...
journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2018-02-12 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.19
更新日期:2012-03-15 00:00:00
abstract::Apoptosis has been established as a mechanism of anti-cancer defense. Members of the BCL-2 family are critical mediators of apoptotic cell death in health and disease, often found to be deregulated in cancer and believed to lead to the survival of malignant clones. However, over the years, a number of studies pointed ...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2015.20
更新日期:2015-03-05 00:00:00
abstract::Traumatic brain injury (TBI) activates multiple neuronal cell death mechanisms, leading to post-traumatic neuronal loss and neurological deficits. TBI-induced cell cycle activation (CCA) in post-mitotic neurons causes regulated cell death involving cyclin-dependent kinase (CDK) activation and initiation of an E2F tran...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1156-y
更新日期:2018-11-06 00:00:00
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
doi:10.1038/cddis.2014.270
更新日期:2014-07-17 00:00:00
abstract::Parkin (Park2), a RING-between-RING-type E3 ubiquitin ligase, has been implicated in regulating NF-κB. Mutations in Parkin are associated with Parkinson's disease. Here we investigated the interaction of Parkin with Receptor-interacting protein kinase 1 (RIPK1) kinase, a key mediator of multiple signaling pathways act...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0770-z
更新日期:2018-06-28 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1417-4
更新日期:2019-02-20 00:00:00
abstract::Ionizing radiation (IR) response has been extensively investigated in BMSCs with an increasing consensus that this type of cells showed relative radiosensitivity in vitro analysis. However, the underlying mechanism of IR-induced injury of BMSCs has not been elucidated. In current study, the regulatory role of miR-22/R...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1373-z
更新日期:2019-03-07 00:00:00
abstract::Osteoblasts and adipocytes are differentiated from common mesenchymal stem cells (MSCs) in processes which are tightly controlled by various growth factors, signaling molecules, transcriptional factors and microRNAs. Recently, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was identified as a ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.485
更新日期:2014-11-20 00:00:00
abstract::The liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0284-8
更新日期:2018-02-14 00:00:00
abstract::H. pylori infection is one of the leading causes of gastric cancer and the pathogenicity of H. pylori infection is associated with its ability to induce chronic inflammation and apoptosis resistance. While H. pylori infection-induced expression of pro-inflammatory cytokines for chronic inflammation is well studied, th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02894-z
更新日期:2020-08-21 00:00:00
abstract::HFM1 (helicase for meiosis 1) is widely recognized as an ATP-dependent DNA helicase and is expressed mainly in germ-line cells. HFM1 is a candidate gene of premature ovarian failure (POF), hence it is also known as POF9. However, the roles of HFM1 in mammalian oocytes remain uncertain. To investigate the functions of ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2697-4
更新日期:2020-06-30 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.396
更新日期:2017-08-31 00:00:00
abstract::TAF6δ is a pro-apoptotic splice variant of the RNA polymerase II general transcription factor, TAF6, that can dictate life vs. death decisions in animal cells. TAF6δ stands out from classical pro-apoptotic proteins because it is encoded by a gene that is essential at the cellular level, and because it functions as a c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0115-3
更新日期:2018-01-22 00:00:00
abstract::Breast cancer is the worldwide leading cause of cancer mortality in women. The majority of deaths from breast cancer arise from metastasis of local tumors. Cancer cells support their rapid proliferation by diverting metabolites into anabolic pathways, but during cancer metastasis, the proliferative program of invasive...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.27
更新日期:2016-03-24 00:00:00
abstract::We demonstrate that EphB3 receptors mediate oligodendrocyte (OL) cell death in the injured spinal cord through dependence receptor mechanism. OLs in the adult spinal cord express EphB3 as well as other members of the Eph receptor family. Spinal cord injury (SCI) is associated with tissue damage, cellular loss and dist...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.262
更新日期:2015-10-15 00:00:00
abstract::Although increasing evidence indicated that deregulation of microRNAs (miRNAs) contributed to tumor initiation and progression, but little is known about the biological role of miR-340 in ovarian cancer (OC). In this study, we found that miR-340 expression was downregulated in OC tissues compared with its expression i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1604-3
更新日期:2019-05-08 00:00:00
abstract::Therapeutic resistance of neoplasms is mainly attributed to gradual evolution of mutational profile1. Here, we demonstrate a microRNA-mediated mechanism that effectively improves fitness of SKBR3 mammary carcinoma cells by cytoplasmic reprogramming. The reprogramming is triggered by endogenous miR4673 transcribed from...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1088-6
更新日期:2018-10-19 00:00:00
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
doi:10.1038/cddis.2016.57
更新日期:2016-03-31 00:00:00
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
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更新日期:2020-04-22 00:00:00
abstract::The acquisition of MDR1-mediated chemoresistance poses a major obstacle to the success of conventional chemotherapeutic agents. HSF1 is also involved in chemoresistance, and several studies have demonstrated the relationship between HSF1 and MDR1 but without any consistent results. Paclitaxel- and doxorubicin-resistan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2600-3
更新日期:2020-05-26 00:00:00