Figure 7.

Multi-target mechanism proposed for 4-NRC-induced apoptosis in multidrug-resistant K562 cells. 4-NRC promotes mitochondrial dysfunction by reduction of mitochondrial activity through loss of Δψ_m and pore formation in the membrane of the mitochondria. Thus, it culminates with an increase of ROS production and cytochrome c release from mitochondria to cytosol and consequent caspase activation to trigger cell apoptosis. In parallel, 4-NRC induces cell cycle arrest at G1/G0 stage due to reduced activity of cyclin D1.