Synthetic molecule uses salt to trigger self-destruction of cancer cells
By Nick Lavars
August 13, 2014
A team of international researchers has developed a molecule capable of triggering cancer cell death by carrying chloride into cancer cell membranes. The molecule flushes the cells with salt and causes them to self-destruct, potentially paving the way for new types of anti-cancer drugs.
The international effort involves researchers from the UK, Texas and South Korea who have collaborated to develop a synthetic ion transporter with a chloride payload. Once it reaches the cancer cells, the chloride interacts with the sodium in the cell membranes and leads to its demise.
"This work shows how chloride transporters can work with sodium channels in cell membranes to cause an influx of salt into a cell," says the University of Southampton's Professor Phillip Gale, one of the study's co-authors. "We found we can trigger cell death with salt.”
The survival of cells in the human body is reliant on the regulation of ions inside their membranes. Upsetting the balance causes them to self-destruct through what is known as apoptosis, a mechanism the body uses to dispose of dangerous or damaged cells.
We have seen apoptosis form the basis of a number of cancer research efforts. The most recent being a cloaked DNA nanodevice that evades the body's immune system to hone in on leukemia and lymphoma cells to activate the suicide switch. The chloride-carrying molecule is the first to demonstrate the effects of salt on cancer cells, however, with the researchers also claiming it could bring benefits to sufferers of cystic fibrosis.
The molecule works by binding to the chloride ions in the cell's membranes. It then draws on the membrane's sodium channels, creating a blanket surrounding the ion and causing it to dissolve. The researchers first found this to be effective in a model with an artificial membrane, a team from South Korea's Yonsei University then tested its efficacy in cultured human cancer cells. An important finding was that the cell's ion balance was disrupted prior to the death of the cell, rather than resulting from the apoptotic process, indicating it was indeed the chloride payload causing its death.
"We have thus closed the loop and shown that this mechanism of chloride influx into the cell by a synthetic transporter does indeed trigger apoptosis," said Professor Jonathan Sessler from the University of Texas and one of the study's co-authors. "This is exciting because it points the way towards a new approach to anticancer drug development."
One complication the researchers will have to overcome for its molecule to be used in cancer treatments is limiting it to cancerous cells. As it stands, the molecule triggers the death of both cancerous and healthy cells so the team will need to modify the synthetic transporter to bind only to the more cancerous ones.
The team's research was published in the journal Nature Chemistry.
Source: University of Southampton