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. 2017 Mar 7;8(17):28154–28168. doi: 10.18632/oncotarget.15962

Figure 3. Mcl-1 acts to suppress mitochondrial ROS production thereby inhibiting CIS.

Figure 3

(A, B) Effects of cytoplasmic ROS-generating enzymes inhibitors on CIS. Cells were pretreated with or without the inhibitors: allopurinol (xanthine oxidase inhibitor); NG-monomethyl-L-arginine (NMMA) (a nitric oxide synthase) or metyrapone (a cytochrome P-450 inhibitor) before or after doxorubicin treatment. The data in A and (C) show that inhibition of mitochondrial and cytoplasmic ROS had no significant effect on the overall levels of ROS in CIS resistant cells after chemotherapy treatment. In CIS-sensitive cells, doxorubicin treatment results in dramatically higher levels of ROS in a time-dependent manner, which are not affected by cytoplasmic inhibitors (B). However, the Mitochondrial ROS inhibitors significantly reduced ROS production in CIS-sensitive cells (D). (E) Quantitative analysis of CIS in Mcl-1-deficient cells with or without the mitochondrial ROS-generating enzyme inhibitors as assessed by γH2AX and PML nuclear body formation. *P < 0.05, comparing those given the indicated inhibitors + doxorubicin to doxorubicin alone. Error bars represent ± S.D. Data are inclusive of at least three independent experiments.