Kill cancer cells by blocking their electrical current

Home >> News Center >> Kill cancer cells by blocking their electrical current

Kill cancer cells by blocking their electrical current

Can cancer cells be killed by cutting off their power supply? This could signal devices that assemble inside tumours to shut down their electrical current and starve them to death.

Starve cancer cells by blocking electron transfer
Frankie Rawson of the University of Nottingham, UK, and his colleagues have detected subtle changes in bioelectric currents from different types of cancer cells. These modifications suggest what metabolic changes have occurred in the cells to allow the rapid division characteristic of cancer.

All biological cells use electrons to feed themselves. In the early 2000s, researchers discovered that cells could also send electrons out of their membranes through biological "relays" made of proteins and other molecules. But we did not know the importance of this trans-plasmatic membrane electron transfer (tPMET). "I think we're just beginning to realize the importance of this process," says Rawson.

People have long suspected that there is a link between how cancer cells change their metabolism to spread and develop and how cells perform this transplasmic electron transfer.

Normal cells produce almost all their energy in the mitochondria, their internal "centres". But mitochondria cannot meet the aggressive requirements of a rapidly dividing cancer cell. This is why cancer cells decrease their mitochondria and accelerate a metabolic pathway called glycolysis, which converts sugar into energy.

Cancer cells eject their electrons using tPMET
The reduction of mitochondrial output creates a problem, as free electrons accumulate inside the cell, blocking the glycolysis process. To avoid starvation, cancer cells eject these extra electrons using tPMET.

"The tPMET is like a safety valve," says Patries Herst of the University of Otago, New Zealand. Indeed, the more invasive and aggressive a cancer is, the more it depends on glycolysis, then tPMET to get rid of electrons.

There are several types of tPMETs with different functions, which made it difficult to study their involvement in tumor growth. "There have been several good investigations," says Lars Jeuken of Leeds University in the United Kingdom. "But no one had ever understood how to directly measure the electron current."

Rawson's team suspected that the strength of these electronic currents could reveal when a cell had become cancerous. "If a cell is under a lot of stress," says Herst, "it means that it uses this system a lot, which could have consequences on the level of aggressiveness and cancer invasion. »

Rawson and colleagues examined the electrical current strength for three different lung cancer cell lines and this showed clear differences, allowing them to determine which cancer cells were metastatic or capable of spreading and which were not invasive.

As the team suspected, when they designed the cells to reduce the number of tPMET relays, their mitochondria were no longer able to produce enough energy and became too heavy. But a surprise awaited them: instead of the expected slowdown in electron transmission, they noticed a "significant increase" in current, said Rawso, with the tPMET cells remaining to eject as many electrons as possible.

Preventing this electron transfer to kill cancer cells
"It was a major discovery for us," says Rawson. "Because if you can prevent this external electron transfer, the cells have limited means to maintain their energy, so they will not be able to proliferate or die.

It also raises another possibility: if we could inhibit electron transfer, we could starve cancer cells. No available drugs can interfere with tPMET, but this new research suggests that we could do it in another way.

Paola Sanjuan-Alberte, also at the University of Nottingham, and Rawson are working on self-assembling nanoelectrodes that could be used as an interface with cancer cells to modify their electrical signalling. These devices would apply an electric field to prevent the relays in a cell from losing power. These devices would apply an electric field to prevent the relays of a cell from losing electrons.