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. Author manuscript; available in PMC: 2020 Jun 4.
Published in final edited form as: Cell Metab. 2019 Feb 28;29(6):1390–1399.e6. doi: 10.1016/j.cmet.2019.02.001

Figure 3. dC Blocks the Uptake and Incorporation of Gem and Other DCK-Activated Pyrimidine-Based Chemotherapies.

Figure 3.

(A) Schematic representation of the mechanism of Gem uptake and metabolism. ENT, equilibrative nucleoside transporter; CNT, concentrative nucleoside transporter; DCK, deoxycytidine kinase; p-Gem, Gem monophosphate; ppp-Gem, Gem triphosphate.

(B) Relative intra and extracellular abundance of Gem in KPC-MT3 cells or media, respectively, after16h of treatment with 6 nM Gem in the presence or absence of 3 μM dC, as measured by LC-MS/MS (n = 3).

(C) Incorporation of Gem into the DNA in KPC-MT3 cells treated with 60 nM 3H-labeled Gem in the presence or absence of dC (n = 3).

(D) Chemical structures of dC and pyrimidine chemotherapies.

(E) Relative viability and IC50 of MT3-KPC cells treated with 5-FU in the presence of 75% TEM CM versus control (n = 3).

(F) Relative viability and IC50 of MT3-KPC cells treated with 5-FU in the presence of 75% 3 μM dC versus control (n = 3).

(G–J) Relative viability and IC50 of MT3-KPC cells treated with 5-aza-cytidine(G), 5-aza-deoxycytidine(H), fialuridine (I), or trifluorothymidine (J) in the presence of 3 μM dC or control (n = 3).

Error bars represent mean ± SD, *p ≤ 0.05; **p ≤ 0.01; ****p ≤ 0.0001. See also Figure S3; Table S3.