|
Type |
Poster Presentation |
Area |
Medicinal Chemistry |
Room No. |
Exhibition Hall 2+3 |
Time |
10월 19일 (목요일) 11:00~12:30 |
Code |
MEDI.P-335 |
Subject |
Synthetic chloride transporters promote apoptotic cell death by disrupting cellular ion homeostasis |
Authors |
Seong-Hyun Park, Injae Shin* Department of Chemistry, Yonsei University, Korea |
Abstract |
Synthetic anion transporters have received attention as anticancer agents because of their potential to disrupt cellular ion homeostasis. However, a direct correlation between a change in cellular chloride anion concentrations and cytotoxicity has not been established for synthetic ion carriers. Here we show that calix[4]pyrrole based transporters induce coupled chloride anion and sodium cation transport in both liposomal models and cells, and promote cell death by increasing intracellular chloride and sodium ion concentrations. Removing either ion from the extracellular media or blocking natural sodium channels with amiloride prevents this effect. Cell experiments show that the ion transporters induce the sodium chloride influx, which leads to release of cytochrome c from the mitochondria and apoptosis via caspase activation. However, they do not activate the caspase-independent apoptotic pathway associated with the apoptosis-inducing factor. Ion transporters, therefore, represent an attractive approach for regulating cellular processes that are normally controlled tightly by homeostasis. |
E-mail |
heaven_bell@yonsei.ac.kr |
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