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Determinants of Ion-Transporter Cancer Cell Death
- Source :
- Chem
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Osmotic shock
General Chemical Engineering
02 engineering and technology
010402 general chemistry
01 natural sciences
Biochemistry
Article
Lysosome
Materials Chemistry
medicine
Environmental Chemistry
Ion transporter
chemistry.chemical_classification
Reactive oxygen species
Biochemistry (medical)
Autophagy
General Chemistry
021001 nanoscience & nanotechnology
0104 chemical sciences
Cell biology
medicine.anatomical_structure
chemistry
Apoptosis
Cancer cell
0210 nano-technology
Intracellular
Subjects
Details
- ISSN :
- 24519294
- Volume :
- 5
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Chem
- Accession number :
- edsair.doi.dedup.....7b72f61d669dcef08250021471134c57