Researchers create synthetic molecule that can cause cancer cells to self-destruction -
The University of Texas at Austin Researchers and five other institutions have created a molecule which can cause cancer cells to self-destruction by transporting the sodium and chloride ions in cancer cells.
These synthetic ion transporters, described this week in the journal Nature Chemistry , confirm a hypothesis than two decades old that could open the way to new cancer drugs while benefiting patients with cystic fibrosis.
synthetic ion transporters have been created before, but this is the first time researchers have shown their work in a real biological system which transported ions obviously cause cells to self-destruction.
cells in the human body work hard to maintain a stable ion concentration within their cell membranes. Disruption of this delicate balance can trigger cells to go through apoptosis, known under the name of programmed cell death, a mechanism that the body uses to get rid of damaged or dangerous cells.
One way to destroy cancer cells would trigger the innate self-destruct sequence by distorting the ion balance in the cells. Unfortunately, when a cell becomes cancerous, it changes the way it carries ions across the cell membrane in a manner which blocks apoptosis.
thereAlmost two decades, a natural substance called prodigiosin was discovered that acted as a natural ion carrier and an anti-cancer effect.
Since then, there has been a "dream chemist," said Jonathan Sessler, professor at the University of Texas at Austin College of Natural Sciences and co-author of the study, to find "carriers man who might be able to do exactly the same job, but better, and also work for the treatment of diseases such as cystic fibrosis, where the chloride channels do not work. "
Sessler and his colleagues, led by professors Shin Injae Yonsei University and Philip A. Gale of Southampton University and King Abdulaziz University, were able to make this dream shape.
The University of Texas team members created a synthetic ion transporter binds chloride ions. The molecule acts in substantially surrounding the chloride ion in an organic cover, which allows to dissolve the ion in the cell membrane, which consists essentially of lipids, or fats. The researchers found that the carrier tends to use the sodium channels that occur naturally in the cell membrane, bringing the sodium ions for the ride.
Gale and his team found that the ion transporters have been effective in a model system using artificial lipid membranes.
Shin and his working group were then able to demonstrate that these molecules promote cell death in human cancer cultured cells. One of the main conclusions is that the cancer cell concentrations of ions changed before apoptosis was triggered, rather than a side effect of cell death.
"So we closed the loop and showed that this influx chloride mechanism in the cell by a synthetic carrier triggers apoptosis indeed," said Sessler. "This is interesting because it shows the way to a new approach for the development of anticancer drugs."
Sessler noted that at present, their synthetic molecule triggers programmed cell death in cancer cells and healthy. To be useful in the treatment of cancer, a version of a chloride transporter anion should be developed which binds only to cancer cells. This could be done by connecting the carrier in question to a site directing molecule such as texaphyrin molecules that Sessler's lab has synthesized.
The results were the culmination of many years of work on three continents and six universities.
"We have shown that this mechanism is viable, this idea has been around for over two decades is scientifically valid, and it's exciting," said Sessler. "We showed sodium will really in chloride will really. There now, I think, very little ambiguity as to the validity of this hypothesis two decades old. "
The next step for researchers will be to take the synthetic ion transporters and test them in animal models.
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