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Teh 2019 Mol Cancer Ther
Additional label Labels  + , 2019-03  +
Coupling states LEAK  + , ROUTINE  + , OXPHOS  + , ET  +
Diseases Cancer  +
Has abstract Metformin has been extensively studied for
Metformin has been extensively studied for its impact on cancer cell metabolism and anticancer potential. Despite evidence of significant reduction in cancer occurrence in diabetic patients taking metformin, phase II cancer trials of the agent have been disappointing, quite possibly because of the lack of molecular mechanism-based patient stratification. In an effort to identify cancers that are responsive to metformin, we discovered that mitochondria respiratory capacity and respiratory reserve, which vary widely among cancer cells, correlate strongly to metformin sensitivity in both the ''in vitro'' and ''in vivo'' settings. A causal relationship between respiratory function and metformin sensitivity is demonstrated in studies in which we lowered respiratory capacity by either genetic knockdown or pharmacologic suppression of electron transport chain components, rendering cancer cells more vulnerable to metformin. These findings led us to predict, and experimentally validate, that metformin and AMP kinase inhibition synergistically suppress cancer cell proliferation. <small>©2019 American Association for Cancer Research.</small>
ciation for Cancer Research.</small>  +
Has editor [[Plangger M]]  +
Has info [https://www.ncbi.nlm.nih.gov/pubmed/30824582 PMID: 30824582 Open Access]  +
Has title Teh JT, Zhu WL, Newgard CB, Casey PJ, Wang M (2019) Respiratory capacity and reserve predict cell sensitivity to mitochondria inhibitors: mechanism-based markers to identify metformin-responsive cancers. Mol Cancer Ther 18:693-705.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  + , Mouse  +
MiP area Respiration  + , Pharmacology;toxicology  +
Pathways N  + , S  + , DQ  + , ROX  +
Preparation Intact cells  + , Permeabilized cells  + , Permeabilized tissue  +
Tissue and cell Other cell lines  +
Was published in journal Mol Cancer Ther +
Was published in year 2019  +
Was written by Teh JT + , Zhu WL + , Newgard CB + , Casey PJ + , Wang M +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
13:58:48, 5 March 2019  +
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