Development of apoptosis-inducing polypeptide via simultaneous mitochondrial membrane disruption and Ca²⁺ delivery.

Abstract

Mitochondria are the primary organelle of regulating apoptosis, and intracellular calcium ions are a key component of pro-apoptosis induction. Herein, we report an artificial apoptosis-inducing polypeptide that destabilizes the mitochondrial membrane and transports calcium ions into the cytosol, thereby synergistically creating severe oxidative conditions. The oxidative stress highly activates an apoptotic signaling cascade, and also inhibits cell migration and invasion in vitro and in vivo. The suggested strategy for simultaneous mitochondrial disruption and perturbed calcium homeostasis demonstrates the applicability of polypeptide-based therapeutics as potent apoptosis-inducers in cancer therapy.