Tubeimoside I-induced lung cancer cell death and the underlying crosstalk between lysosomes and mitochondria.

Abstract:

:Cancer cells have developed chemoresistance and have improved their survival through the upregulation of autophagic mechanisms that protect mitochondrial function. Here, we report that the traditional Chinese anticancer agent tubeimoside I (Tub), which is a potent inhibitor of autophagy, can promote mitochondria-associated apoptosis in lung cancer cells. We found that Tub disrupted both mitochondrial and lysosomal pathways. One of its mechanisms was the induction of DRP1-mediated mitochondrial fragmentation. Another mechanism was the blocking of late-stage autophagic flux via impairment of lysosomal acidification through V-ATPase inhibition; this blocks the removal of dysfunctional mitochondria and results in reactive oxygen species (ROS) accumulation. Excessive ROS accumulation causes damage to lysosomal membranes and increases lysosomal membrane permeability, which leads to the leakage of cathepsin B. Finally, cathepsin B upregulates Bax-mediated mitochondrial outer membrane permeability and, subsequently, cytosolic cytochrome C-mediated caspase-dependent apoptosis. Thus, the cancer cell killing effect of Tub is enhanced through the formation of a positive feedback loop. The killing effect of Tub on lung cancer cells was verified in xenografted mice. In summary, Tub exerts a dual anticancer effect that involves the disruption of mitochondrial and lysosomal pathways and their interaction and, thereby, has a specific and enhanced killing effect on lung cancer cells.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wang K,Zhan Y,Chen B,Lu Y,Yin T,Zhou S,Zhang W,Liu X,Du B,Wei X,Xiao J

doi

10.1038/s41419-020-02915-x

subject

Has Abstract

pub_date

2020-08-26 00:00:00

pages

708

issue

8

issn

2041-4889

pii

10.1038/s41419-020-02915-x

journal_volume

11

pub_type

杂志文章
  • MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro.

    abstract::Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improv...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2367-6

    authors: Yadav SK,Kambis TN,Kar S,Park SY,Mishra PK

    更新日期:2020-03-13 00:00:00

  • Caspase-1 is a novel target of p63 in tumor suppression.

    abstract::p63 is a p53 family transcription factor, which besides unique roles in epithelial development, shares tumor suppressive activity with its homolog p53. The p63 gene has different transcriptional start sites, which generate two N-terminal isoforms (transactivation domain (TA)p63 and amino terminal truncated protein(ΔN)...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.175

    authors: Celardo I,Grespi F,Antonov A,Bernassola F,Garabadgiu AV,Melino G,Amelio I

    更新日期:2013-05-23 00:00:00

  • Tumorigenic potential is restored during differentiation in fusion-reprogrammed cancer cells.

    abstract::Detailed understanding of the mechanistic steps underlying tumor initiation and malignant progression is critical for insights of potentially novel therapeutic modalities. Cellular reprogramming is an approach of particular interest because it can provide a means to reset the differentiation state of the cancer cells ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.189

    authors: Yao J,Zhang L,Hu L,Guo B,Hu X,Borjigin U,Wei Z,Chen Y,Lv M,Lau JT,Wang X,Li G,Hu YP

    更新日期:2016-07-28 00:00:00

  • Ca2+-dependent recruitment of voltage-gated sodium channels underlies bilirubin-induced overexcitation and neurotoxicity.

    abstract::Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neur...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1979-1

    authors: Shi HS,Lai K,Yin XL,Liang M,Ye HB,Shi HB,Wang LY,Yin SK

    更新日期:2019-10-10 00:00:00

  • Adipocytes activate mitochondrial fatty acid oxidation and autophagy to promote tumor growth in colon cancer.

    abstract::Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues o...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.21

    authors: Wen YA,Xing X,Harris JW,Zaytseva YY,Mitov MI,Napier DL,Weiss HL,Mark Evers B,Gao T

    更新日期:2017-02-02 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

    doi:10.1038/s41419-017-0131-3

    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

  • Serum amyloid A inhibits dendritic cell apoptosis to induce glucocorticoid resistance in CD4(+) T cells.

    abstract::Mediators produced by the airway epithelium control the activation, recruitment, and survival of pulmonary dendritic cells (DC) that present antigen to CD4(+) T cells during the genesis and exacerbation of allergic asthma. The epithelial-derived acute phase protein, serum amyloid A (SAA), induces DC maturation and TH1...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.327

    authors: Ather JL,Fortner KA,Budd RC,Anathy V,Poynter ME

    更新日期:2013-09-05 00:00:00

  • Targeting MKK3 as a novel anticancer strategy: molecular mechanisms and therapeutical implications.

    abstract::Mitogen-activated protein kinase kinase 3 (MAP2K3, MKK3) is a member of the dual specificity protein kinase group that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic or stress-inducing stimuli and participates in the MAP kinase-mediated signaling cascade, leading to cell proliferation a...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.591

    authors: Baldari S,Ubertini V,Garufi A,D'Orazi G,Bossi G

    更新日期:2015-01-29 00:00:00

  • Resistance to caspase-8 and -9 fragments in a malignant pleural mesothelioma cell line with acquired cisplatin-resistance.

    abstract::Apoptotic cysteine-aspartate proteases (caspases) are essential for the progression and execution of apoptosis, and detection of caspase fragmentation or activity is often used as markers of apoptosis. Cisplatin (cis-diamminedichloroplatinum (II)) is a chemotherapeutic drug that is clinically used for the treatment of...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2010.54

    authors: Janson V,Johansson A,Grankvist K

    更新日期:2010-09-23 00:00:00

  • Oncogene-dependent function of BRG1 in hepatocarcinogenesis.

    abstract::Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Genomic studies have revealed that HCC is a heterogeneous disease with multiple subtypes. BRG1, encoded by the SMARCA4 gene, is a key component of SWI/SNF chromatin-remodeling complexes. Based on TCGA studies, somatic mutations of SMARCA4 occur ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2289-3

    authors: Wang P,Song X,Cao D,Cui K,Wang J,Utpatel K,Shang R,Wang H,Che L,Evert M,Zhao K,Calvisi DF,Chen X

    更新日期:2020-02-04 00:00:00

  • TIGAR/AP-1 axis accelerates the division of Lgr5- reserve intestinal stem cells to reestablish intestinal architecture after lethal radiation.

    abstract::During radiologic or nuclear accidents, high-dose ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a deadly disorder that urgently needs effective therapy. Unfortunately, current treatments based on natural products and antioxidants have shown very limited effects in alleviating deadly GIS. Reserve i...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2715-6

    authors: Chen F,Zhang Y,Hu S,Shi X,Wang Z,Deng Z,Lin L,Zhang J,Pan Y,Bai Y,Liu F,Zhang H,Shao C

    更新日期:2020-07-06 00:00:00

  • SOCE induced calcium overload regulates autophagy in acute pancreatitis via calcineurin activation.

    abstract::Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by inflammation, edema, vacuolization and necrosis, which has significant morbidity and lethality. The pathogenesis of AP has not been established completely. An early and critical feature of AP is the aberrant signaling of ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0073-9

    authors: Zhu ZD,Yu T,Liu HJ,Jin J,He J

    更新日期:2018-01-19 00:00:00

  • JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry.

    abstract::Mitochondrial membrane potential provides a valuable indicator of cells' health and functional status. Cytometry- and microscopy-based analyses, in combination with fluorescent probes, are widely used to study mitochondrial behavior related to cellular pathways, most notably - apoptosis. The cyanine dye JC-1 (5,5',6,6...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.171

    authors: Perelman A,Wachtel C,Cohen M,Haupt S,Shapiro H,Tzur A

    更新日期:2012-11-22 00:00:00

  • Succinate induces aberrant mitochondrial fission in cardiomyocytes through GPR91 signaling.

    abstract::Altered mitochondrial metabolism acts as an initial cause for cardiovascular diseases and metabolic intermediate succinate emerges as a mediator of mitochondrial dysfunction. This work aims to investigate whether or not extracellular succinate accumulation and its targeted G protein-coupled receptor-91 (GPR91) activat...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0708-5

    authors: Lu YT,Li LZ,Yang YL,Yin X,Liu Q,Zhang L,Liu K,Liu B,Li J,Qi LW

    更新日期:2018-06-04 00:00:00

  • WDR79 promotes the proliferation of non-small cell lung cancer cells via USP7-mediated regulation of the Mdm2-p53 pathway.

    abstract::WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung ca...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.162

    authors: Sun Y,Cao L,Sheng X,Chen J,Zhou Y,Yang C,Deng T,Ma H,Feng P,Liu J,Tan W,Ye M

    更新日期:2017-04-13 00:00:00

  • Human cancer-associated fibroblasts enhance glutathione levels and antagonize drug-induced prostate cancer cell death.

    abstract::Drug resistance is a major problem in cancer therapy. A growing body of evidence demonstrates that the tumor microenvironment, including cancer-associated fibroblasts (CAFs), can modulate drug sensitivity in tumor cells. We examined the effect of primary human CAFs on p53 induction and cell viability in prostate cance...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.225

    authors: Cheteh EH,Augsten M,Rundqvist H,Bianchi J,Sarne V,Egevad L,Bykov VJ,Östman A,Wiman KG

    更新日期:2017-06-01 00:00:00

  • Mitochondrial DNA damage induces apoptosis in senescent cells.

    abstract::Senescence is a cellular response to damage and stress. The senescence response prevents cancer by suppressing the proliferation of cells with a compromised genome and contributes to optimal wound healing in normal tissues. Persistent senescent cells are also thought to drive aging and age-associated pathologies throu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.199

    authors: Laberge RM,Adler D,DeMaria M,Mechtouf N,Teachenor R,Cardin GB,Desprez PY,Campisi J,Rodier F

    更新日期:2013-07-18 00:00:00

  • Organoids as a new model for improving regenerative medicine and cancer personalized therapy in renal diseases.

    abstract::The pressure towards innovation and creation of new model systems in regenerative medicine and cancer research has fostered the development of novel potential therapeutic applications. Kidney injuries provoke a high request of organ transplants making it the most demanding system in the field of regenerative medicine....

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1453-0

    authors: Grassi L,Alfonsi R,Francescangeli F,Signore M,De Angelis ML,Addario A,Costantini M,Flex E,Ciolfi A,Pizzi S,Bruselles A,Pallocca M,Simone G,Haoui M,Falchi M,Milella M,Sentinelli S,Di Matteo P,Stellacci E,Gallucci M,

    更新日期:2019-02-27 00:00:00

  • Wnt signaling induces radioresistance through upregulating HMGB1 in esophageal squamous cell carcinoma.

    abstract::Although many articles have uncovered that Wnt signaling is involved in radioresistance, the mechanism is rarely reported. Here we generated two radioresistant cells rECA109 and rKyse150 from parental esophageal cancer cells ECA109 and Kyse150. We then found that Wnt signaling activity was higher in radioresistant cel...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0466-4

    authors: Zhao Y,Yi J,Tao L,Huang G,Chu X,Song H,Chen L

    更新日期:2018-04-01 00:00:00

  • BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1α stability and MGMT expression.

    abstract::Glioblastoma multiforme (GBM) is the most common brain tumour, characterized by a central and partially necrotic (i.e., hypoxic) core enriched in cancer stem cells (CSCs). We previously showed that the most hypoxic and immature (i.e., CSCs) GBM cells were resistant to Temozolomide (TMZ) in vitro, owing to a particular...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.153

    authors: Persano L,Pistollato F,Rampazzo E,Della Puppa A,Abbadi S,Frasson C,Volpin F,Indraccolo S,Scienza R,Basso G

    更新日期:2012-10-18 00:00:00

  • miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling.

    abstract::Our recent study demonstrated that the QKI-5 regulated miRNA, miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes l...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02997-7

    authors: Huang X,Xiao S,Zhu X,Yu Y,Cao M,Zhang X,Li S,Zhu W,Wu F,Zheng X,Jin L,Xie C,Huang X,Zou P,Li X,Cui R

    更新日期:2020-09-22 00:00:00

  • Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis.

    abstract::This is the first study to investigate the hepatoprotective effect of CQ on acute liver injury caused by carbon tetrachloride (CCl4) in a murine model and the underlying molecular mechanisms. Ninety-six mice were randomly divided into the control (n = 8), CQ (n = 8), CCl4 (n = 40), and CCl4 + CQ (n = 40) treatment gro...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-1136-2

    authors: Dai C,Xiao X,Li D,Tun S,Wang Y,Velkov T,Tang S

    更新日期:2018-11-26 00:00:00

  • Decreased autophagy induced by β1-adrenoceptor autoantibodies contributes to cardiomyocyte apoptosis.

    abstract::It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1-adrenergic receptor autoantibodies (β1-AABs) decreased myocardial autophagy, but the role of decreased auto...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0445-9

    authors: Wang L,Li Y,Ning N,Wang J,Yan Z,Zhang S,Jiao X,Wang X,Liu H

    更新日期:2018-03-14 00:00:00

  • STAT1β enhances STAT1 function by protecting STAT1α from degradation in esophageal squamous cell carcinoma.

    abstract::STAT1, which carries tumor suppressor functions in several models, consists of two isoforms, namely STAT1α and STAT1β. The biological function and significance of STAT1β has never been examined in human cancer. We examined STAT1β function in esophageal squamous cell carcinoma (ESCC) by transfecting a STAT1β gene into ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.481

    authors: Zhang Y,Chen Y,Yun H,Liu Z,Su M,Lai R

    更新日期:2017-10-05 00:00:00

  • circ5615 functions as a ceRNA to promote colorectal cancer progression by upregulating TNKS.

    abstract::Circular RNAs (circRNAs), non-coding RNAs generated by precursor mRNA back-splicing of exons, have been reported to fulfill multiple roles in cancer. However, the role of quite a lot circRNAs in colorectal cancer (CRC) remains mostly unknown. Herein, we explored the expression profiles of circRNAs in 5 paired samples ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2514-0

    authors: Ma Z,Han C,Xia W,Wang S,Li X,Fang P,Yin R,Xu L,Yang L

    更新日期:2020-05-11 00:00:00

  • Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy.

    abstract::Intestinal epithelial cells (IECs) not only have a critical function in the absorption of nutrients, but also act as a physical barrier between our body and the outside world. Damage and death of the epithelial cells lead to the breakdown of this barrier function and inflammation due to access of the immune system to ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.183

    authors: Grabinger T,Luks L,Kostadinova F,Zimberlin C,Medema JP,Leist M,Brunner T

    更新日期:2014-05-15 00:00:00

  • Endoplasmic reticulum stress in bone marrow-derived cells prevents acute cardiac inflammation and injury in response to angiotensin II.

    abstract::Inflammation plays an important role in hypertensive cardiac injury. The endoplasmic reticulum (ER) stress pathway is involved in the inflammatory response. However, the role of ER stress in elevated angiotensin II (Ang II)-induced cardiac injury remains unclear. In this study, we investigated the role of ER stress in...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.164

    authors: Li TT,Jia LX,Zhang WM,Li XY,Zhang J,Li YL,Li HH,Qi YF,Du J

    更新日期:2016-06-09 00:00:00

  • Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors.

    abstract::Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03256-5

    authors: Alaimo A,Lorenzoni M,Ambrosino P,Bertossi A,Bisio A,Macchia A,Zoni E,Genovesi S,Cambuli F,Foletto V,De Felice D,Soldovieri MV,Mosca I,Gandolfi F,Brunelli M,Petris G,Cereseto A,Villarroel A,Thalmann G,Carbone FG,Kr

    更新日期:2020-12-07 00:00:00

  • Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.

    abstract::Histamine is a widely distributed biogenic amine involved in the regulation of an array of biological processes. Serum histamine level is markedly elevated in the early stages of acute myocardial infarction, whereas the role it plays remains unclear. Histidine decarboxylase (HDC) is the unique enzyme responsible for h...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0723-6

    authors: Ding S,Abudupataer M,Zhou Z,Chen J,Li H,Xu L,Zhang W,Zhang S,Zou Y,Hong T,Wang TC,Yang X,Ge J

    更新日期:2018-06-07 00:00:00

  • Mitochondria in skin health, aging, and disease.

    abstract::The skin is a high turnover organ, and its constant renewal depends on the rapid proliferation of its progenitor cells. The energy requirement for these metabolically active cells is met by mitochondrial respiration, an ATP generating process driven by a series of protein complexes collectively known as the electron t...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/s41419-020-2649-z

    authors: Sreedhar A,Aguilera-Aguirre L,Singh KK

    更新日期:2020-06-09 00:00:00