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. Author manuscript; available in PMC: 2021 Jul 27.
Published in final edited form as: Mol Cell. 2020 Dec 30;81(4):691–707.e6. doi: 10.1016/j.molcel.2020.12.012

Figure 3. Interventions that alter NAD+ availability can modulate the antiproliferative effects of PDK inhibition.

Figure 3.

(A) Duroquinone increases NAD+ regeneration via the enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1), which reduces duroquinone to durohydroquinone using NADH as a cofactor.

(B) Proliferation rate of 143B and H1299 cells treated with vehicle (V) or AZD7545 in the absence or presence of duroquinone (20 μM for 143B and 100 μM for H1299 cells; n = 3).

(C) Schematic illustrating the reaction catalyzed by the NADH oxidase from Lactobacillus brevis (LbNOX).

(D) Proliferation rate of 143B and H1299 cells transduced with empty vector (E.V.) or an LbNOX expression vector and treated with vehicle (V) or AZD7545. Doxycycline (500 ng/mL) was included in all conditions (n = 3).

(E) Schematic illustrating the redox consequences of metformin treatment.

(F) Proliferation rate of 143B and H1299 cells treated with 500 μM metformin, AZD7545 (5 μM for 143B, 3 μM for H1299 cells), and 1 mM pyruvate as indicated (n = 3).

Values in panels B, D, and F denote mean ± SD. P values were calculated by unpaired, two-tailed Student’s t-test (n.s. = not significant).