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Fig. 4 | Cancer & Metabolism

Fig. 4

From: Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ß-lapachone

Fig. 4

GLS1 inhibition decreases anti-oxidant defenses and increases susceptibility to ß-lap-induced DNA damage. a Relative NADP+ to NADPH ratio in MiaPaCa2 cells pre-treated with BPTES for 48 h (500 nM) and then treated with ß-lap for 2 h. NADP+ and NADPH levels were measured immediately after 2 h treatment. b Relative extracellular H2O2 was measured through luminescence assay from the media of 4 μM ß-lap ± DIC, ±BPTES-treated MiaPaCa2 over a time-frame of 120 min, ±SE from sextuplicate samples. c Clonogenic survival of MiaPaCa2 pre-treated ± 500 nM BPTES for 48 h followed by the addition of ß-lap for various incubation times. Data represent survival means ± SE from quadruplicate samples. d MiaPaCa2, ASPC1, HPAFII, and MPanc96 pre-treated with ±500 nM BPTES and ±GSH reduced ethyl ester for 48 h followed by the addition of ß-lap for 2 h. e, f Alkaline comet assay of ASPC1 PDA cell lines pre-treated with ±500 nM BPTES followed by 2 h of ß-lap. g Average 53BP1 foci 24 h post treatment in MiaPaCa2. h Western blot for PAR formation with indicated treatment after 15 min of ß-lap exposure. i Relative NAD+ levels ±BPTES with various doses of ß-lap after 2 h of treatment. All results were compared using Student’s t tests. *p < 0.05; **p < 0.01; ***p < 0.001

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