Evidence map›Paper›PMID 21078664›Full record

ArticleThe Journal of biological chemistry2011

Nimbolide sensitizes human colon cancer cells to TRAIL through reactive oxygen species- and ERK-dependent up-regulation of death receptors, p53, and Bax.

Subash C Gupta, Simone Reuter, Kanokkarn Phromnoi, Byoungduck Park, Padmanabhan S Hema, Mangalam Nair, Bharat B Aggarwal

RetractedOpen access · hybridAbstract readRetracted Publication
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 99 citations in OpenAlex.

  1. Vanillin oxime inhibits lung cancer cell proliferation and activates apoptosis through JNK/ERK-CHOP pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021
    Article
  2. Article
  3. Article
  4. Article
  5. EXCLI journal · 2018
    Article
  6. Article
  7. Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).Apoptosis : an international journal on programmed cell death · 2017
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Induction of cell cycle arrest, DNA damage, and apoptosis by nimbolide in human renal cell carcinoma cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  17. Review
  18. Article
  19. Anticancer activity of NOB1-targeted shRNA combination with TRAIL in epithelial ovarian cancer cells.International journal of clinical and experimental pathology · 2015
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Subash C GuptaCytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Simone Reuter
Kanokkarn Phromnoi
Byoungduck Park
Padmanabhan S Hema
Mangalam Nair
Bharat B Aggarwal
The University of Texas MD Anderson Cancer Center · USNational Institute for Interdisciplinary Science and Technology · IN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Kathrin Milbury · 1985 to 2026
$290.8M
TARGETING NF-KB ACTIVATION IN REGULATION OF SYMPTOMS IN PATIENTS WITH MULTIPLEP01CA124787 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI JOHNSON, VALEN EARL · 2008 to 2012
$10.6M
NCI NIH HHS CA016672NCI NIH HHS CA-124787-01A2NCI NIH HHS P01 CA124787NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) shows promise as a cancer treatment, but acquired tumor resistance to TRAIL is a roadblock. Here we investigated whether nimbolide, a limonoid, could sensitize human colon cancer cells to TRAIL. As indicated by assays that measure esterase activity, sub-G(1) fractions, mitochondrial activity, and activation of caspases, nimbolide potentiated the effect of TRAIL. This limonoid also enhanced expression of death receptors (DRs) DR5 and DR4 in cancer cells. Gene silencing of the receptors reduced the effect of limonoid on TRAIL-induced apoptosis. Using pharmacological inhibitors, we found that activation of ERK and p38 MAPK was required for DR up-regulation by nimbolide. Gene silencing of ERK abolished the enhancement of TRAIL-induced apoptosis. Moreover, our studies indicate that the limonoid induced reactive oxygen species production, which was required for ERK activation, up-regulation of DRs, and sensitization to TRAIL; these effects were mimicked by H(2)O(2). In addition, nimbolide down-regulated cell survival proteins, including I-FLICE, cIAP-1, cIAP-2, Bcl-2, Bcl-xL, survivin, and X-linked inhibitor of apoptosis protein, and up-regulated the pro-apoptotic proteins p53 and Bax. Interestingly, p53 and Bax up-regulation by nimbolide was required for sensitization to TRAIL but not for DR up-regulation. Overall, our results indicate that nimbolide can sensitize colon cancer cells to TRAIL-induced apoptosis through three distinct mechanisms: reactive oxygen species- and ERK-mediated up-regulation of DR5 and DR4, down-regulation of cell survival proteins, and up-regulation of p53 and Bax.

Indexed as

AdenocarcinomaAntineoplastic AgentsApoptosisbcl-2-Associated X ProteinBreast NeoplasmsColonic NeoplasmsExtracellular Signal-Regulated MAP KinasesHCT116 CellsHT29 CellsHumansKidney NeoplasmsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLimoninsLung NeoplasmsMultiple MyelomaPancreatic NeoplasmsAntineoplastic Agentsbcl-2-Associated X ProteinExtracellular Signal-Regulated MAP KinasesLimoninsnimbolideReactive Oxygen SpeciesReceptors, TNF-Related Apoptosis-Inducing LigandTNF-Related Apoptosis-Inducing LigandTNFRSF10A protein, humanTNFSF10 protein, humanTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID21078664
PMCPMC3020720
OpenAlexW1984778420

What OpenQuestion holds

Textmetadata
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.