The proposed signaling pathway triggered by NB and Cur in combination in A375 cells.

<p>NB increases the cellular uptake of Cur, which subsequently improves intracellular ROS generation. Overproduction of ROS leads to accumulation of DNA damage. DNA damage activates p53 pathway, which causes mitochondrial dysfunction. Mitochondrial dysfunction activates several caspase cascades, and finally leads to cell apoptosis. In addition, ROS also enhances the phosphorylation of JNK and inactivation of Akt and ERK, which enhances the p53 activation and promotes the apoptotic cascade.