Combination effect of metformin and lansoprazole, proton pump inhibitor, on cell death of MCF7 and MDA-MB 231.
Choi, Yong Won; Lim, In Kyoung
Department of Biochemistry & Molecular Biology
It has been recently reported that metformin, widely used as an antidiabetic drug, reduces risk of cancer development in human and animals based on its inhibitory effects observed in the several cancer cells and mouse tumor models. On the other hand, the vacuolar ATPases are ATP-dependent proton pumps, which induce acidification of the intracellular compartments as opposed to the pumping H+ ions out of the plasma membranes. The pumps play a pivotal role in the regulation of cellular pH in normal cells in addition of tumor cells with greater extent. Recent study reveals that proton pump inhibitors, as the antivaculolar-ATPases, efficiently block H+ transporters in vitro and in vivo, and resulting in cancer cell death.
. ? Because metformin enhances glycolysis and lactic acidosis in cancer cells through the inhibition of mitochondrial complex I activity, pH regulation may be more important to maintain cancer cells survived after treatment with metformin. In the present study, the combined effects of metformin with proton pump inhibitors were investigated in MCF7 and MDA-MB 231 breast cancer cells by employing trypan blue exclusion assay, immunocytochemistry of mitochondrial damage, and in vitro clonogenecity analysis. The viability of cancer cells treated with metformin became more sensitive to the treatment with proton pump inhibitors. We are going to discuss about the molecular mechanism of the combined treatment and its effects in the cancers.
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