A Working Hypothesis of ROCK Inhibition-induced Anti-apoptotic Mechanism in Human CSCs under Dox-treatment.

The apoptotic pathways are commonly agreed to consist of the extrinsic and intrinsic pathways[25]. Chemotherapeutic drug (e.g., Dox)-induced apoptosis likely involves both pathways and a Caspase-independent route[26]. Inhibition of ROCK I and II result in the attenuation of Dox-induced apoptosis. Notes: ADF/Cofilin: actin depolymerizing factor Cofilin protein; Bak: Bcl-2 homologous antagonist/killer; Bid: BH3 interacting-domain death agonist; Bim: Bcl-2 interacting mediator of cell death; Cyt C: Cytochrome C; DISC: death-inducing signaling complex; GEF: Rho guanine nucleotide exchange factor; LIMK1/2: LIM kinase-1 & -2; p-MLC: phosphorylated myosin light chain; Mt: Mitochondria; PTEN: Phosphatase and tension homologue; ROS: Reactive oxygen species; TNFαR: Tumor necrosis factor-α receptor; For other abbreviations, please see Fig 7 and the main text.