Evidence map›Paper›PMID 30621095›Full record

ArticleInternational journal of molecular sciences2019

Metformin Results in Diametrically Opposed Effects by Targeting Non-Stem Cancer Cells but Protecting Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma.

Selena Z Kuo, Christine O Honda, Wei Tse Li, Thomas K Honda, Elizabeth Kim, Xabier Altuna, Eric Abhold, Jessica Wang-Rodriguez, Weg M Ongkeko

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

Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

9 citing papers in PubMed, 21 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

9 authors at 3 institutions in 2 countries.

Selena Z KuoDepartment of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92093, USA. selenazkuo@gmail.com.
Christine O HondaDepartment of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92093, USA. christinehonda70@gmail.com.
Wei Tse LiDepartment of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92093, USA. wtl008@ucsd.edu.
Thomas K HondaDepartment of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92093, USA. thomashonda@sandiego.edu.
Elizabeth KimDepartment of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92093, USA. elizabethkim2011@gmail.com.
Xabier AltunaHospital Donosita, 20014 Donostia, Gipuzkoa, Spain. XABIER.ALTUNAMARIEZCURRENA@osakidetza.net.
Eric AbholdDepartment of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92093, USA. eabhold@gmail.com.
Jessica Wang-RodriguezVeterans Administration Medical Center and Department of Pathology, University of California, San Diego, CA 92092, USA. jessica.wang-rodriguez@va.gov.
Weg M OngkekoDepartment of Otolaryngology-Head and Neck Surgery, University of California, San Diego, CA 92093, USA. wongkeko@ucsd.edu.
University of California, San Diego · USDonostia Unibertsitate Ospitalea · ESUniversity of California San Diego Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer stem cells (CSCs) have been shown as a distinct population of cancer cells strongly implicated with resistance to conventional chemotherapy. Metformin, the most widely prescribed drug for diabetes, was reported to target cancer stem cells in various cancers. In this study, we sought to determine the effects of metformin on head and neck squamous cell carcinoma (HNSCC). CSCs and non-stem HNSCC cells were treated with metformin and cisplatin alone, and in combination, and cell proliferation levels were measured through MTS assays. Next, potential targets of metformin were explored through computational small molecule binding analysis. In contrast to the reported effects of metformin on CSCs in other cancers, our data suggests that metformin protects HNSCC CSCs against cisplatin in vitro. Treatment with metformin resulted in a dose-dependent induction of the stem cell genes CD44, BMI-1, OCT-4, and NANOG. On the other hand, we observed that metformin successfully decreased the proliferation of non-stem HNSCC cells. Computational drug⁻protein interaction analysis revealed mitochondrial complex III to be a likely target of metformin. Based on our results, we present the novel hypothesis that metformin targets complex III to reduce reactive oxygen species (ROS) levels, leading to the differential effects observed on non-stem cancer cells and CSCs.

Indexed as

Biomarkers, TumorCell DeathCell Line, TumorCell ProliferationCisplatinCytoprotectionElectron Transport Complex IIIGene Expression Regulation, NeoplasticHumansMetforminNeoplastic Stem CellsProtein SubunitsSquamous Cell Carcinoma of Head and NeckBiomarkers, TumorCisplatinElectron Transport Complex IIIMetforminProtein Subunitscancer stem cellshead and neck squamous cell carcinomametforminreactive oxygen species

Identifiers

PMID30621095
PMCPMC6337486
OpenAlexW2907426308

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.