دورية أكاديمية
MATE2 expression is associated with cancer cell response to metformin
| العنوان: | MATE2 expression is associated with cancer cell response to metformin |
|---|---|
| المؤلفون: | Chowdhury, Sanjana, Yung, Eric, Pintilie, Melania, Muaddi, Hala, Chaib, Selim, Yeung, Man Tek, Fusciello, Manlio, Sykes, Jenna, Pitcher, Bethany, Hagenkort, Anna, McKee, Trevor, Vellanki, Ravi, Chen, Eric, Bristow, Robert G., Wouters, Bradly G., Koritzinsky, Marianne |
| المصدر: | Chowdhury , S , Yung , E , Pintilie , M , Muaddi , H , Chaib , S , Yeung , M T , Fusciello , M , Sykes , J , Pitcher , B , Hagenkort , A , McKee , T , Vellanki , R , Chen , E , Bristow , R G , Wouters , B G & Koritzinsky , M 2016 , ' MATE2 expression is associated with cancer cell response to metformin ' , PLoS ONE , vol. 11 , no. 12 , e0165214 . https://doi.org/10.1371/journal.pone.0165214Test |
| سنة النشر: | 2016 |
| المجموعة: | The University of Manchester: Research Explorer - Publications |
| مصطلحات موضوعية: | ResearchInstitutes_Networks_Beacons/mcrc, Manchester Cancer Research Centre |
| الوصف: | Background: There is great interest in repurposing the commonly prescribed anti-diabetic drug metformin for cancer therapy. Intracellular uptake and retention of metformin is affected by the expression of organic cation transporters (OCT) 1-3 and by multidrug and toxic compound extrusion (MATE) 1-2. Inside cells, metformin inhibits mitochondrial function, which leads to reduced oxygen consumption and inhibition of proliferation. Reduced oxygen consumption can lead to improved tumor oxygenation and radiation response. Purpose: Here we sought to determine if there is an association between the effects of metformin on inhibiting oxygen consumption, proliferation and expression of OCTs and MATEs in a panel of 19 cancer cell lines. Results: There was relatively large variability in the anti-proliferative response of different cell lines to metformin, with a subset of cell lines being very resistant. In contrast, all cell lines demonstrated sensitivity to the inhibition of oxygen consumption by metformin, with relatively small variation. The expression of OCT1 correlated with expression of both OCT2 and OCT3. OCT1 and OCT2 were relatively uniformly expressed, whereas expression of OCT3, MATE1 and MATE2 showed substantial variation across lines. There were statistically significant associations between resistance to inhibition of proliferation and MATE2 expression, as well as between sensitivity to inhibition of oxygen consumption and OCT3 expression. One cell line (LNCaP) with high OCT3 and low MATE2 expression in concert, had substantially higher intracellular metformin concentration than other cell lines, and was exquisitely sensitive to both anti-proliferative and anti-respiratory effects. In all other cell lines, the concentration of metformin required to inhibit oxygen consumption acutely in vitro was substantially higher than that achieved in the plasma of diabetic patients. However, administering anti-diabetic doses of metformin to tumor-bearing mice resulted in intratu-moral accumulation of metformin and ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1371/journal.pone.0165214 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0165214Test https://research.manchester.ac.uk/en/publications/2703defa-1711-4bae-8be7-f62f973ab78eTest http://www.scopus.com/inward/record.url?scp=85006059589&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.25E843D1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pone.0165214 |
|---|