Evidence map›Paper›PMID 22421144›Full record

ArticleCell cycle (Georgetown, Tex.)2012

Metformin suppresses growth of human head and neck squamous cell carcinoma via global inhibition of protein translation.

Arron Sikka, Manjinder Kaur, Chapla Agarwal, Gagan Deep, Rajesh Agarwal

Open access · bronzeAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

51 citing papers in PubMed, 96 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Association of Diabetes with Oral Cancer- an Enigmatic Correlation.Asian Pacific journal of cancer prevention : APJCP · 2020
    Article
  14. Article
  15. Review
  16. Article
  17. Impact of metformin on disease control and survival in patients with head and neck cancer: a retrospective cohort study.Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale · 2019
    Article
  18. Article
  19. Article
  20. 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

5 authors at 4 institutions in 1 country.

Arron SikkaDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, CO, USA.
Manjinder Kaur
Chapla Agarwal
Gagan Deep
Rajesh Agarwal
Denver School of Nursing · USThe Medical Center of Aurora · USUniversity of Colorado Cancer Center · USUniversity of Colorado System · US

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Prostate cancer prevention and treatment by sillibininR01CA102514 · NCI · UNIVERSITY OF COLORADO DENVER · PI AGARWAL, RAJESH · 2003 to 2013
$3.6M
Skin Cancer Chemoprevention by Silibinin: Mechanisms and EfficacyR01CA140368 · NCI · UNIVERSITY OF COLORADO DENVER · PI AGARWAL, RAJESH · 2010 to 2021
$3.6M
Colon Cancer Chemoprevention by Flavonoid SilibininR01CA112304 · NCI · UNIVERSITY OF COLORADO DENVER · PI AGARWAL, RAJESH · 2005 to 2015
$2.9M
NCI NIH HHS CA102514NCI NIH HHS CA140368NCI NIH HHS P30 CA046934NCI NIH HHS R01 CA102514NCI NIH HHS R01 CA112304NCI NIH HHS R01 CA140368
6 · The paper itself

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer in the world; the main risk factors are alcohol and tobacco use. Advancements in therapies have yet to improve the prognosis of HNSCC. The connection between diabetes and cancer is being recognized, and metformin has been shown to decrease cancer incidence in diabetic patients. Accordingly, here, for the first time, we investigated metformin's efficacy on the growth and viability of human HNSCC FaDU and Detroit cells. Our results show that metformin treatment (5-20 mM) dose-dependently inhibits the growth of both cell lines. In FaDU cells, metformin caused 18-57% and 35-81% growth inhibition after 48 and 72 h treatments, respectively. Similarly, in Detroit 562 cells, 48 and 72 h metformin treatment resulted in 20-57% and 33-82% inhibition, respectively. Mechanistically, metformin caused G 1 arrest, which coincided with a decrease in the protein levels of CDKs (2, 4 and 6), cyclins (D1 and E) and CDK inhibitors (p15, p16, p18 and p27), but no change in p19 and p21. Metformin also decreased the levels of oncogenic proteins Skp2 and β-Trcp. In other studies, metformin decreased the phosphorylation of 4E-BP1 at Ser65, Thr37/46 and Thr70 sites, but drastically increased the phosphorylation of EF2 at Thr56 and AMPK at Thr172, which results in global translational inhibition. In summary, the observed wide spectrum of mechanistic effects of metformin on HNSCC cells provides support for the anticancer capability of the drug and its potential use in future therapies.

Indexed as

beta-Transducin Repeat-Containing ProteinsCarcinoma, Squamous CellCell Line, TumorCell ProliferationCyclin D1Cyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18Cyclin-Dependent Kinase Inhibitor p27Cyclin EG1 Phase Cell Cycle CheckpointsHead and Neck NeoplasmsHumansbeta-Transducin Repeat-Containing ProteinsBTRC protein, humanCDK2 protein, humanCDK4 protein, humanCDK6 protein, humanCDKN2A protein, humanCyclin D1Cyclin-Dependent Kinase 2Cyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18Cyclin-Dependent Kinase Inhibitor p27Cyclin EMetforminNeoplasm Proteinsrho GTP-Binding ProteinsS-Phase Kinase-Associated Proteins

Identifiers

PMID22421144
PMCPMC3350878
OpenAlexW2020226666

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.