Pushing Cancer’s Self-Destruct Button

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An international team of scientists have discovered a potential way to trigger cell death in human cancer cells. The team, which includes researchers from the University of Southampton alongside those from the University of Texas and Yonsei University in Seoul, South Korea, have successfully shown that an influx of sodium chloride using synthetic “transporter” molecules can trigger cell death in human cancer cells.

Cells in the body need to maintain a stable concentration of ions within their membranes; if this is compromised, the cell will undergo apoptosis – the name for the process of programmed cell death by which the body can get rid of faulty cells. Usually the cell membrane controls the movement of substances in and out of the cell, but cancerous cells have differences in the way they transport ions across the cell membrane, blocking apoptosis from happening.

What you need is to build a molecule that will help transport the chloride ion into the cell. The cell membrane is made up mostly of lipids (fats), so by essentially surrounding the chloride ions with an organic compound, they are able to be dissolved by the fatty cell membrane. As Professor Philip Gale explains, “the carrier molecule binds [with]chloride, [and]the carrier-chloride complex is lipophilic…” (attracted to lipids) “…so it allows chloride to enter the cell.” Sodium then also enters the cell to balance charge either side of the cell membrane – the usual channel by which sodium ions would enter the cell, only here facilitated by the chloride ions.

The synthetic molecule in this study was created by the team at the University of Texas. Although this has been done before, it has not been possible to show that the cell’s ion concentrations were definitely altered before apoptosis occurred, rather than as an after-effect of cell death, and this is the causal link that the teams at Southampton, Texas and Yonsei have managed to show through their collaborative efforts.

Prof. Gale heads the team at Southampton University who were a part of this research, including postdoctorate researchers Nathalie Busschaert and Wim Van Rossom. The group is focussed on making ion transporters for the potential future use in treatment of diseases such as cancer and cystic fibrosis. Gale explained “it is important to stress that the compounds described… are not selective for cancer cells over healthy cells, so there is more work to do.” He added “Our next goal is to make the compunds selective for cancer cells.”

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