Evidence map›Paper›PMID 22447040›Full record

ArticleJournal of cancer research and clinical oncology2012

Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells.

Shunchao Yan, Xiujuan Qu, Chong'an Xu, Zhitu Zhu, Lingyun Zhang, Ling Xu, Na Song, Yuee Teng, Yunpeng Liu

Open access · greenAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

27 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Expression and Comparison of Cbl-b in Lung Squamous Cell Carcinoma and Adenocarcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Celecoxib sensitizes gastric cancer to rapamycin via inhibition of the Cbl-b-regulated PI3K/Akt pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015
    Article
  16. Article
  17. Article
  18. Bufalin promotes apoptosis of gastric cancer by down-regulation of miR-298 targeting bax.International journal of clinical and experimental medicine · 2015
    Article
  19. Article
  20. Bufalin exerts antitumor effects by inducing cell cycle arrest and triggering apoptosis in pancreatic cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    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

9 authors at 4 institutions in 1 country.

Shunchao YanDepartment of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, China.
Xiujuan Qu
Chong'an Xu
Zhitu Zhu
Lingyun Zhang
Ling Xu
Na Song
Yuee Teng
Yunpeng Liu
First Hospital of China Medical University · CNChina Medical University · CNFourth Affiliated Hospital of China Medical University · CNJinzhou Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTNF-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapeutic agent that preferentially induces apoptosis in cancer cells. However, breast cancer cells are generally resistant to TRAIL. Bufalin is a major active ingredient of the traditional Chinese medicine ChanSu. The present study aimed to assess the synergistic effect of bufalin and TRAIL and elucidate the underlying mechanisms in breast cancer cells.

methodsCell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. The expression of proteins was assayed by flow cytometry and/or Western blotting. Transfection studies were used to determine the involvement of DR4, DR5 and Cbl-b in the synergistic effect of bufalin and TRAIL.

resultsMCF-7 and MDA-MB-231 cells were resistant to TRAIL. Both cell lines were dramatically sensitized to TRAIL-induced apoptosis by bufalin. Further experiments indicated that bufalin up-regulated DR4 and DR5, activated ERK, JNK and p38 MAPK and down-regulated Cbl-b. Blocking the up-regulation of DR4 and DR5 by siRNA rendered cells less sensitive to apoptosis induced by the combination of bufalin and TRAIL. Inhibition of the activation of ERK, JNK and p38 MAPK by specific inhibitors attenuated DR4 and DR5 up-regulation. Moreover, down-regulation of Cbl-b by shRNA led to stronger activation of ERK, JNK and p38 MAPK, more up-regulation of DR4 and DR5, and a stronger synergistic effect of bufalin and TRAIL.

conclusionsBufalin enhanced TRAIL-induced apoptosis by up-regulating the expression of DR4 and DR5. Bufalin-induced down-regulation of Cbl-b contributed to the up-regulation of DR4 and DR5, which might be partially mediated by the activation of ERK, JNK and p38 MAPK.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsApoptosisBlotting, WesternBreast NeoplasmsBufanolidesCell Line, TumorCell ProliferationDown-RegulationDrug SynergismEnzyme InhibitorsFemaleHumansMammary Neoplasms, ExperimentalMiceMice, Inbred BALB CAdaptor Proteins, Signal TransducingbufalinBufanolidesCBLB protein, humanEnzyme InhibitorsMitogen-Activated Protein KinasesProto-Oncogene Proteins c-cblReceptors, TNF-Related Apoptosis-Inducing LigandTNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID22447040
PMCPMC11824588
OpenAlexW2048986808

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.