Evidence map›Paper›PMID 23613836›Full record

ArticlePloS one2013

Targeted apoptotic effects of thymoquinone and tamoxifen on XIAP mediated Akt regulation in breast cancer.

Shashi Rajput, B N Prashanth Kumar, Siddik Sarkar, Subhasis Das, Belal Azab, Prasanna K Santhekadur, Swadesh K Das, Luni Emdad, Devanand Sarkar, Paul B Fisher and 1 more

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

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
44.3field-weighted citation impact, top 1% 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

55 citing papers in PubMed, 117 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

11 authors at 2 institutions in 2 countries.

Shashi RajputSchool of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India.
B N Prashanth Kumar
Siddik Sarkar
Subhasis Das
Belal Azab
Prasanna K Santhekadur
Swadesh K Das
Luni Emdad
Devanand Sarkar
Paul B Fisher
Mahitosh Mandal
Virginia Commonwealth University · USIndian Institute of Technology Kharagpur · IN

Funding

MDA-7: Novel Cancer Therapeutic GeneR01CA097318 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B · 2002 to 2012
$2.8M
Analysis of a novel regulator of hepatocellular carcinomaR01CA138540 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SARKAR, DEVANAND · 2010 to 2014
$1.6M
Pancreatic Cancer Management by Novel Gene Therapy & Dietary AgentsR01CA127641 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B · 2009 to 2012
$1.2M
NCI NIH HHS 1 R01 CA127641NCI NIH HHS 1 R01 CA138540NCI NIH HHS 5 R01 CA097318NCI NIH HHS R01 CA097318NCI NIH HHS R01 CA127641NCI NIH HHS R01 CA138540
6 · The paper itself

Abstract

X-linked inhibitor of apoptosis protein (XIAP) is constitutively expressed endogenous inhibitor of apoptosis, exhibit its antiapoptotic effect by inactivating key caspases such as caspase-3, caspase-7 and caspase-9 and also play pivotal role in rendering cancer chemoresistance. Our studies showed the coadministration of TQ and TAM resulting in a substantial increase in breast cancer cell apoptosis and marked inhibition of cell growth both in vitro and in vivo. Anti-angiogenic and anti-invasive potential of TQ and TAM was assessed through in vitro studies. This novel combinatorial regimen leads to regulation of multiple cell signaling targets including inactivation of Akt and XIAP degradation. At molecular level, TQ and TAM synergistically lowers XIAP expression resulting in binding and activation of caspase-9 in apoptotic cascade, and interfere with cell survival through PI3-K/Akt pathway by inhibiting Akt phosphorylation. Cleaved caspase-9 further processes other intracellular death substrates such as PARP thereby shifting the balance from survival to apoptosis, indicated by rise in the sub-G1 cell population. This combination also downregulates the expression of Akt-regulated downstream effectors such as Bcl-xL, Bcl-2 and induce expression of Bax, AIF, cytochrome C and p-27. Consistent with these results, overexpression studies further confirmed the involvement of XIAP and its regulatory action on Akt phosphorylation along with procaspase-9 and PARP cleavage in TQ-TAM coadministrated induced apoptosis. The ability of TQ and TAM in inhibiting XIAP was confirmed through siRNA-XIAP cotransfection studies. This novel modality may be a promising tool in breast cancer treatment.

Indexed as

AnimalsAntineoplastic AgentsApoptosisbcl-Associated Death ProteinBenzoquinonesBreast NeoplasmsCell CycleCell Line, TumorCell MovementCell ProliferationCell SurvivalDose-Response Relationship, DrugDown-RegulationDrug SynergismFemaleGlycogen Synthase Kinase 3Antineoplastic Agentsbcl-Associated Death ProteinBenzoquinonesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaProto-Oncogene Proteins c-aktTamoxifenthymoquinoneX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID23613836
PMCPMC3629226
OpenAlexW2044219470

What OpenQuestion holds

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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.