Salinomycin and dichloroacetate synergistically inhibit Lewis lung carcinoma cell proliferation, tumor growth and metastasis.

Salinomycin and dichloroacetate synergistically inhibit Lewis lung carcinoma cell proliferation, tumor growth and metastasis. Biochem Biophys Res Commun. 2020 Jan 16;: Authors: Skeberdytė A, Sarapinienė I, Krasko JA, Barakauskienė A, Žilionytė K, Prokarenkaitė R, Sužiedėlis K, Bukelskienė V, Jarmalaitė S Abstract Drug combination is considered to be the cornerstone of cancer treatment. Simultaneous administration of two or more drugs but at lower doses not only increases cytotoxic effects on tumor cells, but also reduces side effects and possibly overcomes drug resistance. Salinomycin is a well-known cancer stem cell killer, and dichloroacetate is a pyruvate dehydrogenase kinase inhibitor that exclusively targets cells with altered mitochondrial activity, a characteristic being common to most of the cancer cells. In our recent study, we have demonstrated that salinomycin exerted a cytotoxic effect on colorectal carcinoma cells in the 2D and 3D cultures and provided evidence that the mechanism of their synergy was mediated by dichloroacetate-dependent inhibition of the activity of multidrug resistance proteins. In the current work, we confirmed the synergistic cytotoxic properties of salinomycin and dichloroacetate in the 2D and 3D cultures of Lewis lung carcinoma (LLC1) cells. To verify if a synergistic effect of these compounds persisted in vivo, we performed series of experiments using a syngeneic LLC1-C57BL/6 mouse mode...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research