Effect of Metformin Jeko and Jurkaf Cells

Background: Metformin has long been presented to have an anti-glycemic effect and consequently is one of the most commonly prescribed drugs for diabetes, predominantly Type II Diabetes. It has been shown to exert its anti-glycemic effect by increasing insulin sensitivity as well as glucose uptake by peripheral tissues. However, the drug has potential for other uses. In addition to Metformin’s established anti-diabetic effects, there has been substantial preclinical evidence put forth presenting it as a potential anti-cancer medication. Metformin has been associated with a reduced risk of developing certain types of cancer, via different molecular pathways, as well as an improvement in overall cancer survival rates in meta-analysis. Individuals with diabetes have been known to also have a higher risk for several types of cancers such as liver, pancreas, and breast. Methods: In order to determine what effect Metformin could have on a common cancer, such as lymphoma, at a cellular level we performed a 14 day experiment on the effect of 3 different doses of Metformin (0mM, 0.025mM, 0.25mM) on two different lymphoid cell lines, Jurkaf and Jeko [Metformin at 0.025mM concentration is physiological]. Samples were collected on Day 3, 7, 10, and 14 and PCR targeted gene expression was subsequently conducted focusing on mitochondrial and apoptosis related genes (such as cytochrome oxidases (COX2 and 4), nuclear respiratory factor (NRF1), apoptosis gene (P53) and other mitochondrial genes such as PGC1A, SOD2, and TFAM)COX4, MT_CO2, NRF1, P53, PGC1A, SOD2, TFAM]. Discussion: for Jeko showed initial mitochondrial gene expression with Metformin The suppression in mRNA gene expression appears to reverse by day 7. By Day 10 there is a uniform upregulation in mRNA expression and the effects stabilized by day 14. Therefore, we concluded that in Jeko cells, upon initial exposure to metformin, show a decrease in mitochondrial biogenesis and increased apoptosis. This initial suppression seems to be replaced by over-expression of mitochondrial genes over a period of time and effects stabilizes by day 10 of exposure. This phenomenon appears to be shown in both cell lines. Our Jurkaf cells showed less consistent mRNA level changes. We plan to corroborate our gene expression findings with Sea-Horse cell respiration studies. Conclusion: we believe that metformin initially causes cellular apoptosis, however subsequently the cells are able to escape that phenomenon by upregulating mitochondrial genes at physiological doses. In order for metformin to be an effective pro-apoptotic agent in a cancer scenarios, brief pulses of supra-physiological doses may be more effective