Inhibition of autophagy enhances the anticancer activity of silver nanoparticles.


:Silver nanoparticles (Ag NPs) are cytotoxic to cancer cells and possess excellent potential as an antitumor agent. A variety of nanoparticles have been shown to induce autophagy, a critical cellular degradation process, and the elevated autophagy in most of these situations promotes cell death. Whether Ag NPs can induce autophagy and how it might affect the anticancer activity of Ag NPs has not been reported. Here we show that Ag NPs induced autophagy in cancer cells by activating the PtdIns3K signaling pathway. The autophagy induced by Ag NPs was characterized by enhanced autophagosome formation, normal cargo degradation, and no disruption of lysosomal function. Consistent with these properties, the autophagy induced by Ag NPs promoted cell survival, as inhibition of autophagy by either chemical inhibitors or ATG5 siRNA enhanced Ag NPs-elicited cancer cell killing. We further demonstrated that wortmannin, a widely used inhibitor of autophagy, significantly enhanced the antitumor effect of Ag NPs in the B16 mouse melanoma cell model. Our results revealed a novel biological activity of Ag NPs in inducing cytoprotective autophagy, and inhibition of autophagy may be a useful strategy for improving the efficacy of Ag NPs in anticancer therapy.






Lin J,Huang Z,Wu H,Zhou W,Jin P,Wei P,Zhang Y,Zheng F,Zhang J,Xu J,Hu Y,Wang Y,Li Y,Gu N,Wen L




Has Abstract


2014-01-01 00:00:00












  • Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas.

    abstract::Neuroblastoma is the most common extracranial solid tumor in childhood. Despite intense multimodal therapy and many improvements through basic scientific and clinical research, the successful response of advanced-stage patients to chemotherapy remains poor. Autophagy is a cytoprotective mechanism that may help advance...


    pub_type: 杂志文章


    authors: Oehme I,Lodrini M,Brady NR,Witt O

    更新日期:2013-12-01 00:00:00

  • How RB1CC1/FIP200 claws its way to autophagic engulfment of SQSTM1/p62-ubiquitin condensates.

    abstract::Macroautophagy/autophagy mediates the degradation of ubiquitinated aggregated proteins within lysosomes in a process known as aggrephagy. The cargo receptor SQSTM1/p62 condenses aggregated proteins into larger structures and links them to the nascent autophagosomal membrane (phagophore). How the condensation reaction ...


    pub_type: 杂志文章


    authors: Turco E,Witt M,Abert C,Bock-Bierbaum T,Su MY,Trapannone R,Sztacho M,Danieli A,Shi X,Zaffagnini G,Gamper A,Schuschnig M,Fracchiolla D,Bernklau D,Romanov J,Hartl M,Hurley JH,Daumke O,Martens S

    更新日期:2019-08-01 00:00:00

  • Secretory autophagy holds the key to lysozyme secretion during bacterial infection of the intestine.

    abstract::In 2013, Dr. Lora Hooper and colleagues described the induction of antibacterial macroautophagy/autophagy in intestinal epithelial cells as a cytoprotective host defense mechanism against invading Salmonella enterica serovar Typhimurium (S. Typhimurium). Canonical autophagy functions in a primarily degradative capacit...


    pub_type: 杂志文章,评审


    authors: Delorme-Axford E,Klionsky DJ

    更新日期:2018-01-01 00:00:00

  • The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4.

    abstract::The proteasome inhibitor bortezomib has shown remarkable clinical success in the treatment of multiple myeloma. However, the efficacy and mechanism of action of bortezomib in solid tumor malignancies is less well understood. In addition, the use of this first-in-class proteasome inhibitor is limited by several factors...


    pub_type: 杂志文章


    authors: Zang Y,Thomas SM,Chan ET,Kirk CJ,Freilino ML,DeLancey HM,Grandis JR,Li C,Johnson DE

    更新日期:2012-12-01 00:00:00

  • Early alterations of autophagy in Huntington disease-like mice.

    abstract::In a recent study, we reported in vivo evidence of early and sustained alterations of autophagy markers in a novel knock-in mouse model of Huntington disease (HD). The novel model is derived from selective breeding of HdhQ150 knock-in mice to generate mice with ~200 CAG/polyglutamine repeats (HdhQ200). HdhQ200 knockin...


    pub_type: 杂志文章


    authors: Heng MY,Detloff PJ,Paulson HL,Albin RL

    更新日期:2010-11-01 00:00:00

  • Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence.

    abstract::Deficiency in decidualization has been widely regarded as an important cause of spontaneous abortion. Generalized decidualization also includes massive infiltration and enrichment of NK cells. However, the underlying mechanism of decidual NK (dNK) cell residence remains largely unknown. Here, we observe that the incre...


    pub_type: 杂志文章


    authors: Lu H,Yang HL,Zhou WJ,Lai ZZ,Qiu XM,Fu Q,Zhao JY,Wang J,Li DJ,Li MQ

    更新日期:2020-11-01 00:00:00

  • Painting a picture of autophagy in Drosophila.

    abstract::Drawing as a way of understanding things better/easier is in human nature, from textbook images through the models and graphical abstracts published in scientific papers to chalk talks during the academic job interview process. As a molecular cell biologist and geneticist, I always find it easier to show a microscopy ...


    pub_type: 评论,社论


    authors: Juhász G

    更新日期:2019-11-01 00:00:00

  • Broadening the therapeutic scope for rapamycin treatment.

    abstract::The role of autophagy in the degradation of aggregate-prone proteins has been well established. As a result, autophagy upregulation has become an attractive therapeutic strategy for the treatment of proteinopathies, a group of diseases caused by the accumulation of mutant misfolded proteins. We have previously shown t...


    pub_type: 杂志文章


    authors: Menzies FM,Rubinsztein DC

    更新日期:2010-02-01 00:00:00

  • TARDBP/TDP-43 regulates autophagy in both MTORC1-dependent and MTORC1-independent manners.

    abstract::In a recent paper we addressed the mechanism by which defective autophagy contributes to TARDBP/TDP-43-mediated neurodegenerative disorders. We demonstrated that TARDBP regulates MTORC1-TFEB signaling by targeting RPTOR/raptor, a key component and an adaptor protein of MTORC1. Loss of TARDBP decreased the mRNA stabili...


    pub_type: 杂志文章


    authors: Ying Z,Xia Q,Hao Z,Xu D,Wang M,Wang H,Wang G

    更新日期:2016-01-01 00:00:00

  • Autophagy: a new player in hepatic stellate cell activation.

    abstract::Hepatic stellate cell (HSC) activation, the transition from a resident quiescent HSC to a myofibroblastic collagen-producing HSC, is a fundamental feature of liver fibrosis. Autophagy has been implicated in major liver pathologies, such as HCV infection and hepatocarcinoma. However, its role in HSC biology is largely ...


    pub_type: 杂志文章


    authors: Thoen LF,Guimarães EL,Grunsven LA

    更新日期:2012-01-01 00:00:00

  • Dual role of Atg1 in regulation of autophagy-specific PAS assembly in Saccharomyces cerevisiae.

    abstract::Most autophagy-related (Atg) proteins are assembled at the phagophore assembly site or pre-autophagosomal structure (PAS), which is a potential site for vesicle formation during vegetative or starvation conditions. To understand the initial step of vesicle formation, it is important to know how Atg proteins are recrui...


    pub_type: 杂志文章


    authors: Cheong H,Klionsky DJ

    更新日期:2008-07-01 00:00:00

  • Double duty of Atg9 self-association in autophagosome biogenesis.

    abstract::The understanding of the membrane flow process during autophagosome formation is essential to illuminate the role of autophagy under various disease-causing conditions. Atg9 is the only identified integral membrane protein required for autophagosome formation, and it is thought to cycle between the membrane sources an...


    pub_type: 杂志文章


    authors: He C,Baba M,Klionsky DJ

    更新日期:2009-04-01 00:00:00

  • DJ-1 regulation of mitochondrial function and autophagy through oxidative stress.

    abstract::The dysregulation of mitochondrial function has been implicated in the pathogenesis of Parkinson disease. Mutations in the parkin, PINK1 and DJ-1 genes all result in recessive parkinsonism. Although the protein products of these genes have not been fully characterized, it has been established that all three contribute...


    pub_type: 杂志文章


    authors: McCoy MK,Cookson MR

    更新日期:2011-05-01 00:00:00

  • ATG7 is dispensable for LC3-PE conjugation in thioglycolate-elicited mouse peritoneal macrophages.

    abstract::Thioglycolate-elicited macrophages exhibit abundant conjugation of LC3 with PE (LC3-II). Among other autophagy-related (ATG) proteins, it is proposed that, like in yeast, both ATG5 and ATG7 are essential for LC3 conjugation. Using atg5-deficient ( -/- ) and atg7-/- macroph...


    pub_type: 杂志文章


    authors: Vujić N,Bradić I,Goeritzer M,Kuentzel KB,Rainer S,Kratky D,Radović B

    更新日期:2021-01-18 00:00:00

  • Clearance of a Hirano body-like F-actin aggresome generated by jasplakinolide.

    abstract::We have reported in a variety of mammalian cells the reversible formation of a filamentous actin (F-actin)-enriched aggresome generated by the actin toxin jasplakinolide (Lázaro-Diéguez et al., J Cell Sci 2008; 121:1415-25). Notably, this F-actin aggresome (FAG) resembles in many aspects the pathological Hirano body, ...


    pub_type: 杂志文章


    authors: Lázaro-Diéguez F,Knecht E,Egea G

    更新日期:2008-07-01 00:00:00

  • Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome.

    abstract::There is overwhelming evidence for an association between impaired mitochondrial function and metabolic syndrome. Mitophagy, a process that selectively removes damaged mitochondria via a specialized form of autophagy, is essential for mitochondrial quality control (mitochondrial QC) and metabolic homeostasis. We thus ...


    pub_type: 杂志文章


    authors: Wu H,Wang Y,Li W,Chen H,Du L,Liu D,Wang X,Xu T,Liu L,Chen Q

    更新日期:2019-11-01 00:00:00

  • Folding into an autophagosome: ATG5 sheds light on how plants do it.

    abstract::Autophagosomes arise in yeast and animals from the sealing of a cup-shaped double-membrane precursor, the phagophore. The concerted action of about 30 evolutionarily conserved autophagy related (ATG) proteins lies at the core of this process. However, the mechanisms allowing phagophore generation and its differentiati...


    pub_type: 杂志文章


    authors: Le Bars R,Marion J,Satiat-Jeunemaitre B,Bianchi MW

    更新日期:2014-10-01 00:00:00

  • The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14.

    abstract::ULK1 (unc-51 like autophagy activating kinase 1), the key mediator of MTORC1 signaling to autophagy, regulates early stages of autophagosome formation in response to starvation or MTORC1 inhibition. How ULK1 regulates the autophagy induction process remains elusive. Here, we identify that ATG13, a binding partner of U...


    pub_type: 杂志文章


    authors: Park JM,Jung CH,Seo M,Otto NM,Grunwald D,Kim KH,Moriarity B,Kim YM,Starker C,Nho RS,Voytas D,Kim DH

    更新日期:2016-01-01 00:00:00

  • Chaperone-mediated autophagy: the heretofore untold story of J. Fred "Paulo" Dice. Interview by Daniel J. Klionsky.

    abstract::The best-characterized process of autophagy is macroautophagy. Many an article or talk has started with the phrase "...macroautophagy, hereafter referred to as autophagy." This one will be different because we are going to learn more about the person most responsible for increasing our understanding of chaperone-media...


    pub_type: 传,历史文章,杂志文章


    authors: Dice JF

    更新日期:2009-11-01 00:00:00

  • Autophagy and post-ischemic conditioning in retinal ischemia.

    abstract::Retinal ischemia is a major cause of vision loss and a common underlying mechanism associated with diseases, such as diabetic retinopathy and central retinal artery occlusion. We have previously demonstrated the robust neuroprotection in retina induced by post-conditioning (post-C), a brief period of ischemia, 24 h, f...


    pub_type: 杂志文章


    authors: Mathew B,Chennakesavalu M,Sharma M,Torres LA,Stelman CR,Tran S,Patel R,Burg N,Salkovski M,Kadzielawa K,Seiler F,Aldrich LN,Roth S

    更新日期:2020-05-26 00:00:00

  • Autophagy modulates SNCA/α-synuclein release, thereby generating a hostile microenvironment.

    abstract::SNCA/α-synuclein aggregation plays a crucial role in synucleinopathies such as Parkinson disease and dementia with Lewy bodies. Aggregating and nonaggregating SNCA species are degraded by the autophagy-lysosomal pathway (ALP). Previously, we have shown that the ALP is not only responsible for SNCA degradation but is a...


    pub_type: 杂志文章


    authors: Poehler AM,Xiang W,Spitzer P,May VE,Meixner H,Rockenstein E,Chutna O,Outeiro TF,Winkler J,Masliah E,Klucken J

    更新日期:2014-01-01 00:00:00

  • The role of MTMR14 in autophagy and in muscle disease.

    abstract::Phosphoinositides (PIs) are a group of low-abundance phospholipids that play a critical role in the control of organelle and membrane traffic. There is strong evidence that specific PIs are also important for the regulation of autophagy. PIs are modified by a complex network of lipid kinases and phosphatases. A recent...


    pub_type: 杂志文章


    authors: Gibbs EM,Feldman EL,Dowling JJ

    更新日期:2010-08-01 00:00:00

  • Friend or food: different cues to the autophagosomal proteome.

    abstract::A hallmark of macroautophagy is the formation of autophagosomes, double-membrane vesicles that enwrap cellular components destined for lysosomal degradation. We examined autophagosomal protein dynamics under various inducing stimuli using a comprehensive mass spectrometry-based proteomics approach in combination with ...


    pub_type: 杂志文章


    authors: Becker AC,Bunkenborg J,Eisenberg T,Harder LM,Schroeder S,Madeo F,Andersen JS,Dengjel J

    更新日期:2012-06-01 00:00:00

  • Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon.

    abstract::ISG15 (ISG15 ubiquitin-like modifier), a ubiquitin-like protein, is one of the major type I IFN (interferon) effector systems. ISG15 can be conjugated to target proteins (ISGylation) via the stepwise action of E1, E2, and E3 enzymes. Conjugated ISG15 can be removed (deISGylated) from target proteins by USP18 (ubiquiti...


    pub_type: 杂志文章


    authors: Xu D,Zhang T,Xiao J,Zhu K,Wei R,Wu Z,Meng H,Li Y,Yuan J

    更新日期:2015-04-03 00:00:00

  • Reticulocyte mitophagy: monitoring mitochondrial clearance in a mammalian model.

    abstract::Mitochondria are the primary site of energy production in animal cells. In mitochondria, the flow of electrons through the electron transport chain creates a potential difference across the inner membrane, which is utilized for ATP production. However, due to inherent inefficiencies in electron transport, reactive oxy...


    pub_type: 杂志文章


    authors: Zhang J,Ney PA

    更新日期:2010-04-01 00:00:00

  • Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/α-tubulin acetylation.

    abstract::Macroautophagy/autophagy, a fundamental process for degradation of macromolecules and organelles, occurs constitutively at a basal level and is upregulated in response to stress. Whether autophagy regulates protein acetylation and microtubule stability in vascular smooth muscle cells (VSMCs) migration, however, remain...


    pub_type: 杂志文章


    authors: Ouyang C,Mu J,Lu Q,Li J,Zhu H,Wang Q,Zou MH,Xie Z

    更新日期:2020-10-01 00:00:00

  • The functions of Atg8-family proteins in autophagy and cancer: linked or unrelated?

    abstract::The Atg8-family proteins are subdivided into two subfamilies: the GABARAP and LC3 subfamilies. These proteins, which are major players of the autophagy pathway, present a conserved glycine in their C-terminus necessary for their association to the autophagosome membrane. This family of proteins present multiple roles ...


    pub_type: 杂志文章


    authors: Jacquet M,Guittaut M,Fraichard A,Despouy G

    更新日期:2020-04-19 00:00:00

  • RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye.

    abstract::Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and ...


    pub_type: 杂志文章


    authors: Muniz-Feliciano L,Doggett TA,Zhou Z,Ferguson TA

    更新日期:2017-01-01 00:00:00

  • Autophagy proteins promote hepatitis C virus replication.

    abstract::Autophagy is a fundamental process for anti-viral defense. Not surprisingly, viruses have developed strategies to subvert or use autophagy for their own benefit. In cell culture, autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection. Autophagy proteins are required for tran...


    pub_type: 杂志文章


    authors: Dreux M,Chisari FV

    更新日期:2009-11-01 00:00:00

  • SPHK1 (sphingosine kinase 1) induces epithelial-mesenchymal transition by promoting the autophagy-linked lysosomal degradation of CDH1/E-cadherin in hepatoma cells.

    abstract::SPHK1 (sphingosine kinase 1), a regulator of sphingolipid metabolites, plays a causal role in the development of hepatocellular carcinoma (HCC) through augmenting HCC invasion and metastasis. However, the mechanism by which SPHK1 signaling promotes invasion and metastasis in HCC remains to be clarified. Here, we repor...


    pub_type: 杂志文章


    authors: Liu H,Ma Y,He HW,Zhao WL,Shao RG

    更新日期:2017-05-04 00:00:00