한빛사 논문
DaeYong Leea, Soo‐Hwan Leeb, Ilkoo Noha, Eonju Ohb, Hyunil Ryuc, JongHoon Haa, SeongDong Jeonga, Jisang Yooa, Tae‐Joon Jeonc, Chae‐Ok Yunb,*, Yeu‐Chun Kima,*
aDepartment of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea
bDepartment of Bioengineering, College of Engineering, Hanyang University, Seoul 04763, Republic of Korea
cDepartment of Biological Engineering, Inha University, Incheon 22212, Republic of Korea
D.Y.L. and S.-H.L. contributed equally to this work.
*To whom correspondence should be addressed.
Abstract
Perturbation of potassium homeostasis can affect various cell functions and lead to the onset of programmed cell death. Although ionophores have been intensively used as an ion homeostasis disturber, the mechanisms of cell death are unclear and the bioapplicability is limited. In this study, helical polypeptide‐based potassium ionophores are developed to induce endoplasmic reticulum (ER) stress‐mediated apoptosis. The polypeptide‐based potassium ionophores disturb ion homeostasis and then induce prolonged ER stress in the cells. The ER stress results in oxidative environments that accelerate the activation of mitochondria‐dependent apoptosis. Moreover, ER stress‐mediated apoptosis is triggered in a tumor‐bearing mouse model that suppresses tumor proliferation. This study provides the first evidence showing that helical polypeptide‐based potassium ionophores trigger ER stress‐mediated apoptosis by perturbation of potassium homeostasis.
Keywords : apoptosis, cancer therapy, ER stress, perturbed potassium homeostasis, potassium ionophore
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