Evidence map›Paper›PMID 18074035›Full record

ArticlePloS one2007

Nitrosylcobalamin potentiates the anti-neoplastic effects of chemotherapeutic agents via suppression of survival signaling.

Joseph A Bauer, Joseph A Lupica, Heidi Szugye, Bei H Morrison, Rebecca M Haney, Rhonda K Masci, Rebecca M Lee, Joseph A Didonato, Daniel J Lindner

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. CD320 Receptor and Vitamin B12 as Potential Targets for Anti-Cancer Therapy.International journal of molecular sciences · 2025
    Review
  4. The human BThe Journal of biological chemistry · 2020
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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.

Joseph A BauerTaussig Cancer Center, Center for Hematology and Oncology Molecular Therapeutics, The Cleveland Clinic Foundation, Cleveland, Ohio, United States of America. bauerj@ccf.org <bauerj@ccf.org>
Joseph A Lupica
Heidi Szugye
Bei H Morrison
Rebecca M Haney
Rhonda K Masci
Rebecca M Lee
Joseph A Didonato
Daniel J Lindner
Cleveland Clinic · USBauer Research Foundation · US

Funding

INFLAMMATION--IKAPPA B KINASE STRUCTURE FUNCTION STUDIESR01CA084406 · NCI · CLEVELAND CLINIC LERNER COL/MED-CWRU · PI DIDONATO, JOSEPH · 2000 to 2004
$1.2M
Inositol hexakisphosphate kinase 2:apoptosis regulatorR01CA095020 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LINDNER, DANIEL J · 2003 to 2006
$1.1M
NCI NIH HHS CA095020NCI NIH HHS CA84406NCI NIH HHS R01 CA084406NCI NIH HHS R01 CA095020
6 · The paper itself

Abstract

backgroundNitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells, based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated apoptosis and inhibits survival signaling in a variety of malignant cell lines. Chemotherapeutic agents often simultaneously induce an apoptotic signal and activation of NF-kappaB, which has the undesired effect of promoting cell survival. The specific aims of this study were to 1) measure the anti-tumor effects of NO-Cbl alone and in combination with conventional chemotherapeutic agents, and to 2) examine the mechanism of action of NO-Cbl as a single agent and in combination therapy. METHODOLOGY: Using anti-proliferative assays, electrophoretic mobility shift assay (EMSA), immunoblot analysis and kinase assays, we demonstrate an increase in the effectiveness of chemotherapeutic agents in combination with NO-Cbl as a result of suppressed NF-kappaB activation.

resultsEighteen chemotherapeutic agents were tested in combination with NO-Cbl, in thirteen malignant cell lines, resulting in a synergistic anti-proliferative effect in 78% of the combinations tested. NO-Cbl pre-treatment resulted in decreased NF-kappaB DNA binding activity, inhibition of IkappaB kinase (IKK) enzymatic activity, decreased AKT activation, increased caspase-8 and PARP cleavage, and decreased cellular XIAP protein levels.

conclusionThe use of NO-Cbl to inhibit survival signaling may enhance drug efficacy by preventing concomitant activation of NF-kappaB or AKT.

Indexed as

Antineoplastic AgentsApolipoproteinsApoptosisCell Line, TumorElectrophoretic Mobility Shift AssayEnzyme ActivationHumansI-kappa B KinaseNF-kappa BNitroso CompoundsProto-Oncogene Proteins c-aktSignal TransductionTNF-Related Apoptosis-Inducing LigandVitamin B 12X-Linked Inhibitor of Apoptosis ProteinAntineoplastic AgentsApolipoproteinsI-kappa B KinaseNF-kappa BNitroso CompoundsnitrosylcobalaminProto-Oncogene Proteins c-aktTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanVitamin B 12XIAP protein, humanX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID18074035
PMCPMC2117345
OpenAlexW2142513773

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.