Figure 2
Role of NADPH oxidases-generated ROS.
(A) Ivermectin-induced ROS are Ca2+–, ATP- and P2X7-regulated. 4T1.2 cells were labeled with a ROS detection probe and treated for 1 h with 32 μM Ivermectin in the presence of 1 mM EDTA, 5 mM NAC, 5 μM DPI, 2500 μunits/ml Apyrase, 3 mM ATP and 10 μM KN-62. (B) Ivermectin-induced cell death is transiently reversed by inhibition of NADPH oxidases with DPI (μM concentrations as indicated). Triangles (▲) indicate significant antagonism CI > 1.0. (C) Synergy between Ivermectin and H2O2- or irradiation-generated ROS, as well as the ROS-inducing chemotherapeutic agents paclitaxel (PTX) and doxorubicin (DOX). 4T1.2 cancer cells were irradiated (10–20 kRad) or treated with H2O2 (10–1000 μM), PTX (0.1–1 μM), or DOX (1–4 μM) and incubated with Ivermectin for 24h/48h. Circles (●) indicate significant synergy CI < 1.0, see Table 1. Asterisk (*) indicates p < 0.05 relative to untreated or Ivermectin alone controls, respectively.
