Determinants of Ion-Transporter Cancer Cell Death.
Determinants of Ion-Transporter Cancer Cell Death.
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DOI：
10.1016/j.chempr.2019.05.001
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发表时间：
2019-08-08
期刊：
影响因子：
23.5
通讯作者：
Shin I
中科院分区：
文献类型：
--
作者：
Park SH;Park SH;Howe ENW;Hyun JY;Chen LJ;Hwang I;Vargas-Zuñiga G;Busschaert N;Gale PA;Sessler JL;Shin I
Recently, we showed that synthetic anion transporters DSC4P-1 and SA-3 had activity related to cancer cell death. They were found to increase intracellular chloride and sodium ion concentrations. They were also found to induce apoptosis (DSC4P-1) and both induce apoptosis and inhibit autophagy (SA-3). However, determinants underlying these phenomenological findings were not elucidated. The absence of mechanistic understanding has limited the development of yet-improved systems. Here, we show that three synthetic anion transporters, DSC4P-1, SA-3, and 8FC4P, induce osmotic stress in cells by increasing intracellular ion concentrations. This triggers the generation of reactive oxygen species via a sequential process and promotes caspase-dependent apoptosis. In addition, two of the transporters, SA-3 and 8FC4P, induce autophagy by increasing the cytosolic calcium ion concentration promoted by osmotic stress. However, they eventually inhibit the autophagy process as a result of their ability to disrupt lysosome function through a transporter-mediated decrease in a lysosomal chloride ion concentration and an increase in the lysosomal pH. Park et al. show that three synthetic ion transporters, SA-3, 8FC4P, and DSC4P-1, promote apoptosis by increasing intracellular sodium and chloride concentrations in cells and consequently inducing osmotic stress. In addition, two of the transporters, SA-3 and 8FC4P, induce autophagy by increasing the cytosolic calcium ion concentration promoted by osmotic stress. However, they eventually inhibit the autophagy process because of their ability to disrupt lysosome function through a transporter-mediated decrease in lysosomal chloride ion concentration and an increase in the lysosomal pH.
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影响因子：
7.7
作者：
He C;Zhu H;Li H;Zou MH;Xie Z
通讯作者：
Xie Z
影响因子：
21.8
作者：
Busschaert N;Park SH;Baek KH;Choi YP;Park J;Howe ENW;Hiscock JR;Karagiannidis LE;Marques I;Félix V;Namkung W;Sessler JL;Gale PA;Shin I
通讯作者：
Shin I
影响因子：
15
作者：
Busschaert, Nathalie;Wenzel, Marco;Light, Mark E.;Iglesias-Hernandez, Paulina;Perez-Tomas, Ricardo;Gale, Philip A.
通讯作者：
Gale, Philip A.
DOI：
10.1083/jcb.200807047
发表时间：
2009-02-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hao JJ;Liu Y;Kruhlak M;Debell KE;Rellahan BL;Shaw S
通讯作者：
Shaw S
影响因子：
64.8
作者：
Graves, Austin R.;Curran, Patricia K.;Mindell, Joseph A.
通讯作者：
Mindell, Joseph A.