The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells

被引:2
|
作者
Nurzhan, Sholpan [1 ,2 ]
Bekezhankyzy, Zhibek [1 ,2 ]
Ding, Hong [3 ]
Berdigaliyev, Nurken [1 ,2 ]
Sergazy, Shynggys [2 ,4 ,5 ]
Gulyayev, Alexander [2 ,4 ,5 ]
Shulgau, Zarina [2 ,4 ]
Triggle, Christopher R. [3 ]
Aljofan, Mohamad [1 ,4 ]
机构
[1] Nazarbayev Univ, Sch Med, Dept Biomed Sci, Z05H0P9, Astana, Kazakhstan
[2] Natl Ctr Biotechnol, Z05K8D5, Astana, Kazakhstan
[3] Qatar Fdn, Weill Cornell Med Qatar, Dept Pharmacol, POB 24144, Doha, Qatar
[4] Nazarbayev Univ, Drug Discovery & Dev Lab, Natl Lab Astana, Z05H0P9, Astana, Kazakhstan
[5] Res Inst Balneol & Med Rehabil, Burabay 021708, Akmola Region, Kazakhstan
关键词
metformin; apoptosis; antiproliferative; mTOR; BCL-2; glucose; OXIDATIVE STRESS; P53; GROWTH; APOPTOSIS; FAMILY; TARGET;
D O I
10.3390/pharmaceutics15092186
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The glucose-lowering drug metformin has been reported to have anticancer properties through unknown mechanisms. Other unknown factors that may influence its anticancer potential include the glycemic status of the patient. Therefore, the objective of this study is to determine the effect of different glucose environments on the antiproliferative potency and the cellular mechanism of action of metformin. Human breast cancer cells, MCF-7, were incubated in low, normal, elevated, and high glucose environments and treated with metformin. The antiproliferative potential of metformin and its effect on protein expression as well as its ability to induce cellular apoptosis and autophagy under different glucose environments, were determined using different molecular techniques. Metformin significantly inhibited cellular proliferation in a time- and glucose-concentration-dependent manner. In comparison to elevated glucose, low normal glucose alone induced a significant level of autophagy that was further increased in the presence of metformin. While glucose concentration did not appear to have an effect on the antiproliferative potency of metformin, the cellular basis of action was shown to be glucose-dependent. The antiproliferative mechanism of action of metformin in elevated and low normal glucose environments is mTOR-dependent, whereas, in the high glucose environment, the antiproliferative mechanism is independent of mTOR. This is the first study to report that both the antiproliferative potency and the cellular mechanism of action aredependent on the concentration of glucose.
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页数:14
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