Salinomycin and dichloroacetate synergistically inhibit Lewis lung carcinoma cell proliferation, tumor growth and metastasis
| Autor: | Ieva Sarapinienė, Sonata Jarmalaitė, Rimvilė Prokarenkaitė, Aistė Skeberdytė, Aušrinė Barakauskienė, Karolina Žilionytė, Jan Aleksander Krasko, Virginija Bukelskienė, Kęstutis Sužiedėlis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Pyruvate dehydrogenase kinase Biophysics Apoptosis Biochemistry udc:616.24-006.6 Lung neoplasms drug therapy Carcinoma lewis lung Pyrans pharmacology Dichloroacetic acid Cell line tumor drug effects Drug synergism Metastasis Carcinoma Lewis Lung 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cancer stem cell Cell Line Tumor Biomarkers Tumor medicine Animals Cytotoxic T cell Neoplasm Metastasis 616.24-006.6 [udc] Molecular Biology Salinomycin Cell Proliferation Dichloroacetic Acid Cell growth Lewis lung carcinoma Drug Synergism Cell Biology medicine.disease Mice Inbred C57BL 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer cell Neoplastic Stem Cells Cancer research |
| Zdroj: | Biochemical and biophysical research communications, San Diego : Elsevier, 2020, vol. 523, no. 4, p. 874-879 |
| ISSN: | 0006-291X 1090-2104 |
| Popis: | 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 model and demonstrated that combination therapy with salinomycin and DCA increased the survival rate of allografted mice, inhibited metastatic site formation and reduced the populations of cancer stem cells as well as cells that underwent the epithelial-to-mesenchymal transition. Our results demonstrate that a synergistic effect of salinomycin and dichloroacetate exists not only in vitro but also in vivo and suggest their benefits in the treatment of metastatic cancers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect