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. 2018 Dec 11;25(11):3047–3058.e4. doi: 10.1016/j.celrep.2018.11.043

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© 2018 The Authors

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

Dual MCT1 and MCT4 Inhibition Is Necessary to Kill Cancer Cells

(A and B) Survival curve of HAP1 MCT1-KO cells with increasing concentrations of syrosingopine (S; in A) and the MCT1 inhibitor ARC155858 (AR; in B). Both drugs were also titrated in the presence of a sub-lethal concentration of metformin (M, 4 mM) to elicit possible synthetic lethality.

(C and D) Survival curve for HAP1 MCT4-KO cells treated with syrosingopine (C) and ARC155858 (D).

(E–H) Human cancer cell lines comprising all combinations of MCT1 and MCT4 expression. HL60 (E), K562 (F), SkBr3 (G), and MDA-MD-453 (H) were titrated with increasing concentrations of ARC155858 in the presence of sub-lethal concentrations of metformin (4 mM) or syrosingopine (0.5 μM). Cell proliferation and survival was measured after 3 days. All data points are in triplicate and presented as mean ± SEM.