Inhibition of Survival Pathways MAPK and NF-kB Triggers Apoptosis in Pancreatic Ductal Adenocarcinoma Cells via Suppression of Autophagy

Papademetrio, Daniela L.; Lompardía, Silvina; Simunovich, Tania; Costantino, Susana N.; Mihalez, Cintia; Cavaliere, Victoria; Álvarez, Élida

doi:10.1007/s11523-015-0388-3

Cited by 60 publications

(46 citation statements)

References 64 publications

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“…A previous study reported that the positive feedback loop between autophagy and the NF-κB signaling cascade might exacerbate the inflammation induced by H5N1 pseudotyped viral particles [28]. The inhibition of NF-κB was also documented to induce autophagy suppression, leading to apoptosis in pancreatic ductal adenocarcinoma cells [52]. We speculate that autophagy and inflammatory cascade reactions might be positively regulated by PEDV infection to exacerbate inflammation.…”

Section: Discussionmentioning

confidence: 69%

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

Guo

Zhang

et al. 2017

Viruses

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The new porcine epidemic diarrhea (PED) has caused devastating economic losses to the swine industry worldwide. Despite extensive research on the relationship between autophagy and virus infection, the concrete role of autophagy in porcine epidemic diarrhea virus (PEDV) infection has not been reported. In this study, autophagy was demonstrated to be triggered by the effective replication of PEDV through transmission electron microscopy, confocal microscopy, and Western blot analysis. Moreover, autophagy was confirmed to benefit PEDV replication by using autophagy regulators and RNA interference. Furthermore, autophagy might be associated with the expression of inflammatory cytokines and have a positive feedback loop with the NF-κB signaling pathway during PEDV infection. This work is the first attempt to explore the complex interplay between autophagy and PEDV infection. Our findings might accelerate our understanding of the pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.

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Section: Discussionmentioning

confidence: 69%

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

Guo

Zhang

et al. 2017

Viruses

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“…NF-κB is a transcription factor connected with several cellular processes such as inflammation, proliferation, apoptosis and development (Wang et al, 2008c; Meng et al, 2011; Sarode et al, 2015; Papademetrio et al, 2016). NF-κB comprises of five members, RelA (p65), RelB, c-Rel, p50, and p52 (Sun et al, 2013).…”

Section: Tgr5 and Cell Signalingmentioning

confidence: 99%

TGR5, Not Only a Metabolic Regulator

2016

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G-protein-coupled bile acid receptor, Gpbar1 (TGR5), is a member of G-protein-coupled receptor (GPCR) superfamily. High levels of TGR5 mRNA were detected in several tissues such as small intestine, stomach, liver, lung, especially in placenta and spleen. TGR5 is not only the receptor for bile acids, but also the receptor for multiple selective synthetic agonists such as 6α-ethyl-23(S)-methyl-cholic acid (6-EMCA, INT-777) and a series of 4-benzofuranyloxynicotinamde derivatives to regulate different signaling pathways such as nuclear factor κB (NF-κB), AKT, and extracellular signal-regulated kinases (ERK). TGR5, as a metabolic regulator, is involved in energy homeostasis, bile acid homeostasis, as well as glucose metabolism. More recently, our group and others have extended the functions of TGR5 to more than metabolic regulation, which include inflammatory response, cancer and liver regeneration. These findings highlight TGR5 as a potential drug target for different diseases. This review summarizes the basic information of TGR5 and its new functions.

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“…CAPE inhibits EMT in PaCa and is a potent apoptosisinducing agent (118). Its antiproliferative activity may involve the induction of mitochondrial dysfunction and the activation of caspase-3/caspase-7 (119). CAPE induces apoptosis after autophagy inhibition in a caspase-dependent and a caspase-independent manner in PaCa cells (120).…”

Section: Egcgmentioning

confidence: 99%

Pancreatic Cancer Stem Cells and Therapeutic Approaches

Ercan

Karlıtepe

Özpolat³

2017

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Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest human cancers, with 1-5% 5-year survival rates (~6-month median survival duration) despite therapy; thus, PDAC represents an unmet therapeutic challenge. PDAC is the major histological subtype, comprising 90% of all pancreatic cancers. It is a highly complex and aggressive malignancy, presenting with early local invasion and metastasis, and is resistant to most therapies, all of which are believed to contribute to its extremely poor prognosis. PDAC is characterized by molecular alterations, including mutations of K-RAS (~90% of cases), TP53, transforming growth factor-β, Hedgehog, WNT and NOTCH signaling pathways. Given that cancer stem cells have a crucial role not only in tumor initiation and progression, but also in drug resistance and relapse or recurrence of various cancer types, they may be excellent targets for effective novel therapeutic approaches. Here, we reviewed recent therapeutic strategies targeting pancreatic cancer stem cells using chemotherapeutics and targeted drugs, non-coding RNAs (i.e., siRNA and miRNAs), immunotherapy, and natural compounds.

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Inhibition of Survival Pathways MAPK and NF-kB Triggers Apoptosis in Pancreatic Ductal Adenocarcinoma Cells via Suppression of Autophagy

Abstract: Here we present evidence that allows us to consider a combined therapy regimen comprising an autophagy inhibitor and a MAPK or NF-kB pathway inhibitor as a possible treatment strategy for pancreatic cancer.

Cited by 60 publications

References 64 publications

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

TGR5, Not Only a Metabolic Regulator

Pancreatic Cancer Stem Cells and Therapeutic Approaches

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