Combination therapy of metformin with sodium selenite reverses effects of monotherapy on nitric oxide production, IL-1β and TNF-α release, and upregulates relative expression of Bcl-2 by LPS-activated human primary monocytes in T-cell acute lymphoblastic leukemia

ObjectivesWe examined the influence of the ex vivo combination therapy of metformin (Met, 1,1-dimethylbiguanide hydrochloride) with sodium selenite (Ss, Na2SeO3) on the changes in the production of nitric oxide (NO) and selected cytokines by circulating monocytes (MOs) during T-cell acute lymphoblastic leukemia (T-ALL). MethodsAssays were performed on MO cell samples isolated from children with T-ALL. ResultsMet+Ss combination therapy reversed the Ss effect on the upregulation of NO production. Both Met+Ss and Ss treatment alone induced a significant downregulation of extracellular calcium ions consumption (ecCa2+) levels. Additionally, Met treatment induced a significant upregulation of IL-1{beta} and TNF- production; such effects were significantly reversed after combination with Ss treatment. Moreover, Met+Ss induced no significant effect on the production of IL-10, IL-6 and TNF-, but a slight increase in IFN-{gamma} levels. Furthermore, treatment with Ss alone induced a slight increase of IFN-{gamma}. Finally, Met+Ss induced a marked upregulation of relative Bcl-2 expression in MOs. ConclusionsMet+Ss combination therapy results in downregulation of NO production, IL-1{beta} and TNF- release as well as in upregulation of the relative expression levels of Bcl-2-associated survival of primary MOs in human T-ALL.