Figure 1. Intrinsic and extrinsic apoptotic signaling pathways.

Anticancer agents target and interfere with the intrinsic and extrinsic signaling pathways. Upon treatment with tumor cells, anticancer agents induce ROS generation which eventually leads to damage of the mitochondrial membrane. Activated Bak/Bax results in mitochondrial permeabilization. Damaged mitochondrial membrane results in the release of cyt c, which triggers the activation of caspase-mediated apoptosis. Endoplasmic reticulum (ER) stress causes the discharge of calcium ions, which activates the m-calpain caspase-mediated apoptotic pathway. ER stress release activating transcription factor 6 alpha (Atf6-α) leading to apoptosis via activation of C/EBP homologous protein (CHOP). In the extrinsic pathway, the induction of death-inducing signaling complex (DISC) associated caspase 8 with the activation of apoptosis effector protein caspase 3 as well as BH3-only pro-apoptotic protein Bid to its active form tBid subsequently stimulates the multidomain pro-apoptotic proteins (Bax/Bak) to exhibit their activities.