Evidence map›Paper›PMID 27821095›Full record

ArticleBMC cancer2016

Treatment of a chemoresistant neuroblastoma cell line with the antimalarial ozonide OZ513.

Don W Coulter, Timothy R McGuire, John G Sharp, Erin M McIntyre, Yuxiang Dong, Xiaofang Wang, Shawn Gray, Gracey R Alexander, Nagendra K Chatuverdi, Shantaram S Joshi and 2 more

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

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 84% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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

12 authors at 2 institutions in 1 country.

Don W CoulterCollege of Medicine, Division of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
Timothy R McGuireDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA. trmcguir@unmc.edu.
John G SharpDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Erin M McIntyreDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Yuxiang DongDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Xiaofang WangDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Shawn GrayDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Gracey R AlexanderDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Nagendra K ChatuverdiCollege of Medicine, Division of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
Shantaram S JoshiDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Xiaoyu ChenDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Jonathan L VennerstromDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
University of Nebraska Medical Center · USNebraska Medical Center · US

Funding

Research Pilot Project ProgramP30GM106397 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI JOHNSON, KEITH R · 2013 to 2017
$4.9M
NIGMS NIH HHS P30 GM106397
6 · The paper itself

Abstract

backgroundEvaluate the anti-tumor activity of ozonide antimalarials using a chemoresistant neuroblastoma cell line, BE (2)-c.

methodsThe activity of 12 ozonides, artemisinin, and two semisynthetic artemisinins were tested for activity against two neuroblastoma cell-lines (BE (2)-c and IMR-32) and the Ewing's Sarcoma cell line A673 in an MTT viability assay. Time course data indicated that peak effect was seen 18 h after the start of treatment thus 18 h pre-treatment was used for all subsequent experiments. The most active ozonide (OZ513) was assessed in a propidium iodide cell cycle flow cytometry analysis which measured cell cycle transit and apoptosis. Metabolic effects of OZ513 in BE (2)-c cells was evaluated. Western blots for the apoptotic proteins cleaved capase-3 and cleaved PARP, the highly amplified oncogene MYCN, and the cell cycle regulator CyclinD1, were performed. These in-vitro experiments were followed by an in-vivo experiment in which NOD-scid gamma immunodeficient mice were injected subcutaneously with 1 × 10

resultsIt was confirmed that five commonly used chemotherapy drugs had no cytotoxic activity in BE (2)-c cells. Six of 12 ozonides tested were active in-vitro at concentrations achievable in vivo with OZ513 being most active (IC50 = 0.5 mcg/ml). OZ513 activity was confirmed in IMR-32 and A673 cells. The Ao peak on cell-cycle analysis was increased after treatment with OZ513 in a concentration dependent fashion which when coupled with results from western blot analysis which showed an increase in cleaved capase-3 and cleaved PARP supported an increase in apoptosis. There was a concentration dependent decline in the MYCN and a cyclinD1 protein indicative of anti-proliferative activity and cell cycle disruption. OXPHOS metabolism was unaffected by OZ513 treatment while glycolysis was increased. There was a significant delay in time to tumor development in mice treated with OZ513 and a decline in the rate of tumor growth.

conclusionsThe antimalarial ozonide OZ513 has effective in-vitro and in-vivo activity against a pleiotropic drug resistant neuroblastoma cell-line. Treatment with OZ513 increased apoptotic markers and glycolysis with a decline in the MYCN oncogene and the cell cycle regulator cyclinD1. These effects suggest adaptation to cellular stress by mechanism which remain unclear.

Indexed as

AnimalsAntimalarialsAntineoplastic AgentsApoptosisArtemisininsBiomarkersCaspase 3Cell CycleCell Line, TumorDisease Models, AnimalDrug Resistance, NeoplasmHeterocyclic CompoundsHumansMetabolomeMetabolomicsMice1,2,4-trioxaneAntimalarialsAntineoplastic AgentsartemisininArtemisininsBiomarkersCaspase 3Heterocyclic CompoundsCell cycleMetabolismNeuroblastomaOzonide antimalarials

Identifiers

PMID27821095
PMCPMC5100253
OpenAlexW2549507965

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.