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. 2017 Mar 6;8(20):32576–32585. doi: 10.18632/oncotarget.15936

Figure 4. NADPH accumulation is responsible for apoptosis.

Figure 4

(A and B) Effects of trolox, BHA, NAC and DPI on NADPH/NADP+ ratio in MCF-7 and MDA-MB-231 cells induced by cerulenin or orlistat. NADPH/NADP+ was measured after cells were treated with 10 μM of cerulenin or 100 μg/ml of orlistat in combination with 2 mM of trolox, 10 mM of NAC, 100 μM of BHA or 5 μM of DPI for 2 h. (C and D) Effects of DPI on ROS generation in MCF-7 and MDA-MB-231 cells induced by cerulenin and orlistat. ROS levels were measured after cells were treated with 10 μM of cerulenin or 100 μg/ml of orlistat in combination with 5μM of DPI for 2 h. (E and F) Effects of DPI on apoptosis in MCF-7 and MDA-MB-231 cells induced by cerulenin and orlistat. Apoptosis was measured after cells were treated with 10 μM of cerulenin or 100 μg/ml of orlistat in combination with 5 μM of DPI for 48 h. Error bar indicates ± SE (n = 3). *p < 0.05; **p < 0.01 (t-test). (G) DPI and orlistat synergistically suppressed tumor growth of MDA-MB-231 cells in a xenograft model. (H) A model to show the mechanism underlying FAS inhibition-induced apoptosis.