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. 2021 Sep 3;81(20):5202–5216. doi: 10.1158/0008-5472.CAN-21-2734

Figure 3.

Figure 3. Oncogenic HSP90 inhibition decreases the synthesis of DNA, proteins, and biomass gain. A, Cartoon showing changes in selected metabolites from anabolic mitochondrial and pentose phosphate pathways and their metabolic fate in OCI-Ly1 and OCI-Ly7 cells. B, Glucose carbon tracing in OCI-Ly1 cells treated with vehicle or the oncogenic HSP90 inhibitor PU-H71 for 30 minutes, 3 hours, and 6 hours. The primary glucose-derived isotope for each metabolite is shown as relative to glucose m+6. The metabolite is indicated on top as glucose 6-phosphate (G6P), fructose 6-phosphate (F6P), glyceraldehyde 3-phosphate (G3P), ribose 5-phosphate (R5P), and citrate. C, Left, detection of newly synthesized protein by the incorporation rate of the amino acid analogue L-homoproparglyglycine in OCI-Ly1 and OCI-Ly7 cells treated with vehicle or PU-H71 0.5 μmol/L for 6 hours. Right, detection of newly synthesized DNA by the incorporation rate of thymidine analogue 5-ethynyl-2′-deoxyuridine in OCI-Ly1 and OCI-Ly7 cells treated with vehicle or PU-H71 0.5 μmol/L for 6 hours. In all panels, error bars are SEM of three independent experiments. D, Real-time assessment at single-cell resolution of cellular MAR in OCI-Ly1 cells treated with vehicle and upon administration of PU-H71 to the same culture. Bottom, mean MAR comparing binned datasets. P values were calculated by t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Oncogenic HSP90 inhibition decreases the synthesis of DNA, proteins, and biomass gain. A, Cartoon showing changes in selected metabolites from anabolic mitochondrial and pentose phosphate pathways and their metabolic fate in OCI-Ly1 and OCI-Ly7 cells. B, Glucose carbon tracing in OCI-Ly1 cells treated with vehicle or the oncogenic HSP90 inhibitor PU-H71 for 30 minutes, 3 hours, and 6 hours. The primary glucose-derived isotope for each metabolite is shown as relative to glucose m+6. The metabolite is indicated on top as glucose 6-phosphate (G6P), fructose 6-phosphate (F6P), glyceraldehyde 3-phosphate (G3P), ribose 5-phosphate (R5P), and citrate. C, Left, detection of newly synthesized protein by the incorporation rate of the amino acid analogue L-homoproparglyglycine in OCI-Ly1 and OCI-Ly7 cells treated with vehicle or PU-H71 0.5 μmol/L for 6 hours. Right, detection of newly synthesized DNA by the incorporation rate of thymidine analogue 5-ethynyl-2′-deoxyuridine in OCI-Ly1 and OCI-Ly7 cells treated with vehicle or PU-H71 0.5 μmol/L for 6 hours. In all panels, error bars are SEM of three independent experiments. D, Real-time assessment at single-cell resolution of cellular MAR in OCI-Ly1 cells treated with vehicle and upon administration of PU-H71 to the same culture. Bottom, mean MAR comparing binned datasets. P values were calculated by t test. *, P < 0.05; **, P < 0.01; ***, P < 0.001.