FIGURE 1.

Cell death mechanisms. (A) Concept of the activation of programmed cell death pathway in cancer treatment. Illustration of the concept that anti-cancer drug/agents activate steps leading to activation of a step in the cellular regulatory pathway leading to programmed cell death is presented. It is generally considered that anti-cancer drugs/agents kill cancer cells by activating an intrinsic programmed cell death pathway, involving the leaking of mitochondrial cytochrome C, assembly of Apaf-1 into apoptosomes, activation of caspase 9 and subsequently caspase 3, leading to widespread proteolytic destruction of proteins and cellular structure, and ultimately cell death. (B) Puncture of plasma membrane and nuclear envelope in necroptosis. Necroptosis is a caspase-independent programmed cell death mechanism. Cellular signaling (such as cytokines) activates RIPK1 and then RIPK3 kinases, which phosphorylates MLKL. The phosphorylated MLKL polymerizes and assembles into a pore/channel that can insert onto the nuclear or plasma membrane, leading to membrane puncture and the leaking of nuclear or cellular components, ultimately causing cell death. (C) Taxane-induced irreversible membrane rupture. A more recent understanding is that paclitaxel (taxanes) kills cancer cell by inducing the formation of multiple micronuclei (micronucleation) and consequently causing the irreversible membrane rupture of the micronuclei. Taxanes induce the micronucleation and cell death by both mitotic and non-mitotic mechanisms.