Abstract:
:Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. In this study, we examined whether the PPARγ-activated pathway contributed to the antitumor effect of two cannabinoids, Δ9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC cells. Both cannabinoids increased the activity and intracellular level of PPARγ mRNA and protein, which was abolished by the PPARγ inhibitor GW9662. Moreover, genetic ablation with small interfering RNA (siRNA), as well as pharmacological inhibition of PPARγ decreased the cannabinoid-induced cell death and apoptosis. Likewise, GW9662 totally blocked the antitumoral action of cannabinoids in xenograft-induced HCC tumors in mice. In addition, PPARγ knockdown with siRNA caused accumulation of the autophagy markers LC3-II and p62, suggesting that PPARγ is necessary for the autophagy flux promoted by cannabinoids. Interestingly, downregulation of the endoplasmic reticulum stress-related protein tribbles homolog 3 (TRIB3) markedly reduced PPARγ expression and induced p62 accumulation, which was counteracted by overexpression of PPARγ in TRIB3-knocked down cells. Taken together, we demonstrate for the first time that the antiproliferative action of the cannabinoids THC and JWH-015 on HCC, in vitro and in vivo, are modulated by upregulation of PPARγ-dependent pathways.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Vara D,Morell C,Rodríguez-Henche N,Diaz-Laviada Idoi
10.1038/cddis.2013.141subject
Has Abstractpub_date
2013-05-02 00:00:00pages
e618issn
2041-4889pii
cddis2013141journal_volume
4pub_type
杂志文章abstract::Autophagy (macroautophagy) is an evolutionarily conserved lysosomal degradation process, in which a cell degrades long-lived proteins and damaged organelles. Recently, accumulating evidence has revealed the core molecular machinery of autophagy in carcinogenesis; however, the intricate relationship between autophagy a...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2013.422
更新日期:2013-10-31 00:00:00
abstract::Cancer-initiating cell (CIC) is critical in cancer development, maintenance and recurrence. The reverse expression pattern of coxsackie and adenovirus receptor (CAR) and αν integrin in bladder cancer decreases the infection efficiency of adenovirus. We constructed Arg-Gly-Asp (RGD)-modified oncolytic adenovirus, carry...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Alzheimer's disease (AD) is pathologically characterised by the age-dependent deposition of β-amyloid (Aβ) in senile plaques, intraneuronal accumulation of tau as neurofibrillary tangles, synaptic dysfunction and neuronal death. Neuroinflammation, typified by the accumulation of activated microglia and reactive astroc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.50
更新日期:2011-06-02 00:00:00
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
doi:10.1038/s41419-020-02864-5
更新日期:2020-08-19 00:00:00
abstract::The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a key component of tumor necrosis factor (TNF)-induced necroptosis and plays a crucial role in necroptosis execution. However, the mechanisms that control MLKL activity are not completely understood. Here, we identify the molecular chaperone Hsp90 as ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.390
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abstract::Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic ...
journal_title:Cell death & disease
pub_type: 杂志文章
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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
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abstract::This study aimed to evaluate treatment response, survival, safety profiles, and predictive factors to chimeric antigen receptor T cell (CAR-T) therapy in Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL). 39R/R B-ALL patients who underwent CAR-T therapy were included. Baseline ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2388-1
更新日期:2020-03-30 00:00:00
abstract::Death-associated protein kinase 1 (DAPK1, DAPk, DAPK) is known for its involvement in apoptosis and autophagy-associated cell death. Here, we identified an unexpected function of DAPK1 in suppressing necroptosis. DAPK1-deficiency renders macrophages and dendritic cells susceptible to necroptotic death. We also observe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2534-9
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abstract::Inhibitor of Apoptosis Proteins act as E3 ubiquitin ligases to regulate NF-κB signalling from multiple pattern recognition receptors including NOD2, as well as TNF Receptor Superfamily members. Loss of XIAP in humans causes X-linked Lymphoproliferative disease type 2 (XLP-2) and is often associated with Crohn's diseas...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0508-y
更新日期:2018-05-01 00:00:00
abstract::Patients with high-grade serous ovarian cancer (HGSC) frequently receive platinum-based chemotherapeutics, such as cisplatin. Cisplatin binds to DNA and induces DNA-damage culminating in mitochondria-mediated apoptosis. Interestingly, mitochondrial DNA is critically affected by cisplatin but its relevance in cell deat...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2081-4
更新日期:2019-11-07 00:00:00
abstract::Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-s...
journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2013.248
更新日期:2013-07-11 00:00:00
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
更新日期:2020-03-13 00:00:00
abstract::Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.211
更新日期:2015-08-13 00:00:00
abstract::Mitochondrial dysfunction and synaptic damage are critical early features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and τ. We previously reported that the scaffolding protein RanBP9, which is overall increased in AD, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.203
更新日期:2013-01-24 00:00:00
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
doi:10.1038/s41419-018-0757-9
更新日期:2018-06-27 00:00:00
abstract::Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.381
更新日期:2017-08-17 00:00:00
abstract::Adaptive responses of skeletal muscle regulate the nuclear shuttling of the sarcomeric protein Ankrd2 that can transduce different stimuli into specific adaptations by interacting with both structural and regulatory proteins. In a genome-wide expression study on Ankrd2-knockout or -overexpressing primary proliferating...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.525
更新日期:2014-01-16 00:00:00
abstract::Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.88
更新日期:2011-09-08 00:00:00
abstract::Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viab...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.144
更新日期:2016-05-26 00:00:00
abstract::Mitochondrial Lon is a multi-function matrix protease with chaperone activity. However, little literature has been undertaken into detailed investigations on how Lon regulates apoptosis through its chaperone activity. Accumulating evidences indicate that various stresses induce transportation of p53 to mitochondria an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0730-7
更新日期:2018-06-13 00:00:00
abstract::Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy, whereas no effective interventions are available. Andrographolide, an active component extracted from Andrographis paniculate, is prescribed as a treatment for upper respiratory tract infection. Here we rep...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2195-8
更新日期:2019-12-20 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is involved in insulin resistance (IR) and diabetic retinopathy. In retinal pigment epithelial (RPE) cells, insulin activates the mTOR pathway, inducing hypoxia-inducible factor-1α (HIF-1α) and HIF-dependent transcription in serum-free minimum essential medium Eagle (MEM). Serendip...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.178
更新日期:2014-05-08 00:00:00
abstract::The anti-apoptotic protein MCL-1 is a key regulator of cancer cell survival and a known resistance factor for small-molecule BCL-2 family inhibitors such as ABT-263 (navitoclax), making it an attractive therapeutic target. However, directly inhibiting this target requires the disruption of high-affinity protein-protei...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.561
更新日期:2015-01-15 00:00:00
abstract::Mucin is an important physical barrier against enteric pathogens. VvpE is an elastase encoded by Gram-negative bacterium Vibrio vulnificus; however, the functional role of VvpE in intestinal mucin (Muc) production is yet to be elucidated. The recombinant protein (r) VvpE significantly reduced the level of Muc2 in huma...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.152
更新日期:2015-06-18 00:00:00
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
doi:10.1038/s41419-019-2015-1
更新日期:2019-10-14 00:00:00
abstract::Although accumulating evidence has linked mesenchymal stem cells (MSCs) with tumor growth, the underlying mechanisms are poorly understood. Here, we demonstrated for the first time that human umbilical cord MSCs (hUCMSCs) dramatically increased the growth of lung adenocarcinoma (LUAD) cancer cells in a xenograft tumor...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0323-5
更新日期:2018-02-13 00:00:00
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
更新日期:2018-11-26 00:00:00
abstract::The growing number of studies suggested that inhibition of autophagy enhances the efficacy of Akt kinase inhibitors in cancer therapy. Here, we provide evidence that ML-9, a widely used inhibitor of Akt kinase, myosin light-chain kinase (MLCK) and stromal interaction molecule 1 (STIM1), represents the 'two-in-one' com...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.156
更新日期:2014-04-24 00:00:00
abstract::The formulation of quercetin nanoliposomes (QUE-NLs) has been shown to enhance QUE antitumor activity in C6 glioma cells. At high concentrations, QUE-NLs induce necrotic cell death. In this study, we probed the molecular mechanisms of QUE-NL-induced C6 glioma cell death and examined whether QUE-NL-induced programmed c...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.242
更新日期:2013-08-01 00:00:00