Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291, Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea.
Department of Bioengineering, College of Engineering, Hanyang University, 222, Wangsimni-ro Seongdong-gu, Seoul, Republic of Korea.
Biomaterials. 2019 Mar;197:51-59. doi: 10.1016/j.biomaterials.2019.01.006. Epub 2019 Jan 4.
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.
线粒体是调控细胞凋亡的主要细胞器，细胞内钙离子是诱导细胞凋亡的关键组成部分。在此，我们报告了一种人工诱导凋亡的多肽，它可以破坏线粒体膜并将钙离子转运到细胞质中，从而协同产生严重的氧化应激。氧化应激强烈激活凋亡信号级联反应，并抑制体外和体内的细胞迁移和侵袭。同时破坏线粒体和扰乱钙稳态的策略表明，基于多肽的治疗方法作为癌症治疗中有效的凋亡诱导剂具有适用性。
