Evidence map›Paper›PMID 34678726›Full record

ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2021

Nuclear factor kappa-B contributes to cigarette smoke tolerance in pancreatic ductal adenocarcinoma through cysteine metabolism.

Venugopal Gunda, Yashpal S Chhonker, Nagabhishek Sirpu Natesh, Pratima Raut, Sakthivel Muniyan, Todd A Wyatt, Daryl J Murry, Surinder K Batra, Satyanarayana Rachagani

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Venugopal GundaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Yashpal S ChhonkerDepartment of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Nagabhishek Sirpu NateshDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Pratima RautDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Sakthivel MuniyanDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Todd A WyattVeterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA; Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Daryl J MurryDepartment of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred & Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Satyanarayana RachaganiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: srachagani@unmc.edu.
University of Nebraska Medical Center · USNebraska Medical Center · US

Funding

Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Targeting CXCR2 axis in Pancreatic CancerR01CA228524 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., SINGH, RAKESH K · 2018 to 2022
$2.0M
Rac1 GTPase in tumorigenesis and progression of pancreatic cancerR01CA206444 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., OUELLETTE, MICHEL M · 2016 to 2020
$1.9M
Targeting tumor and its microenvironment using nanotherapeutics for pancreatic cancerR01CA247763 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI RACHAGANI, SATYANARAYANA · 2020 to 2024
$1.9M
Altered Histidine Metabolism in Pancreatic Cancer: A Novel Metabolic Target to Enhance Gemcitabine EfficacyR21CA238953 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI RACHAGANI, SATYANARAYANA, VISWANATHAN, SARASWATHI · 2019 to 2020
$372k
NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA206444NCI NIH HHS R01 CA228524NCI NIH HHS R01 CA247763NCI NIH HHS R21 CA238953
6 · The paper itself

Abstract

backgroundRetrospective studies revealed that cigarette smoking enhances risk of incidence and worsens prognosis in pancreatic cancer (PC) patients. Poor prognosis in smoker cohort of PC patients indicates prevalence of cigarette smoke stimulated survival mechanisms yet to be explored in PC. In this study, cigarette smoke induced metabolic pathways were explored and targeted in PC.

methodsHuman pancreatic ductal adenocarcinoma cell (PDAC) lines, genetically engineered mice models (GEMMs), mass spectrometry based heavy isotope-based metabolite analysis, cytotoxicity assays and Nuclear factor kappa-B (NF-kB) targeting were utilized in this study. Cigarette smoke extract (CSE) was prepared fresh each day by bubbling cell culture media with the smoke emitted from 85 mm, filtered, Code 1R6F reference cigarettes and used for in vitro procedures. High dose cigarette smoke exposure of GEMMs was achieved by daily exposure of animals to similar cigarettes, 6 h/day for a total period of 180 days.

findingsWe observed that PDAC cells upregulate glutathione anabolism through cysteine uptake and glutamate cysteine ligase (GCLM), supporting survival, upon CSE exposure. In vivo, cigarette smoke exposure leads to concomitant upregulation of GCLM and activated NF-kB in the PDAC consistent with in vitro, in CSE-exposed PDAC. Finally, either inhibition of NF-kB or depletion of cysteine impaired PDAC cell survival in cigarette smoke exposed conditions through suppression of glutathione and ROS enhancement, reverted by glutathione supplementation.

interpretationOur findings demonstrate scope for targeting smoke induced, NF-kB mediated, cysteine and glutathione metabolism for improving the survival of smoke addicted PDAC.

Indexed as

AnimalsCarcinoma, Pancreatic DuctalCell Line, TumorCysteineGlutamate-Cysteine LigaseGlutathioneHumansMetabolomeMice, TransgenicNF-kappa BPancreatic NeoplasmsReactive Oxygen SpeciesSmokeTobacco ProductsCysteineGCLM protein, humanGlutamate-Cysteine LigaseGlutathioneNF-kappa BReactive Oxygen SpeciesSmokecigarette smokecysteineglutathioneNF-κBpancreatic cancer

Identifiers

PMID34678726
PMCPMC8599650
OpenAlexW3205694763

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.