August 27, 2012

Activating An Enzyme Stops Cancerous Tumors From Forming

Lee Rannals for — Your Universe Online

Boosting the activity of a particular enzyme can help block tumors from growing, according to research published in Nature Chemical Biology.

Cancer cells use up most of their energy by reproducing themselves, but in order to do this they must produce new cellular building blocks like DNA, carbohydrates and lipids.

Biologists found that jacking up the activity of the enzyme pyruvate kinase can disrupt the production of tumors forming in mice.

“It´s fair to say that perhaps activating pyruvate kinase could have some role in pushing tumors away from a program that allows them to efficiently grow,” Vander Heiden, the Howard S. and Linda B. Stern Career Development Assistant Professor of Biology at MIT, said in a press release. “Whether or not it would really be a viable drug in people is an open question.”

The enzyme controls one of the final steps of glycolysis, which breaks down the molecule of glucose to produce two molecules of ATP, which is the cell's energy currency.

In healthy cells, the end product of glycolysis, called pyruvate, enters another pathway that creates more ATP.

As cells become more cancerous, they start to express another enzyme that is a form of pyruvate kinase called PKM2. This version is less active than its PKM1 counterpart, and its low activity allows glycolysis to be diverted into metabolic pathways that build new building blocks.

“Normal cells don´t need to build things, they just need to keep the lights on. They just burn energy to keep things running, whereas cancer cells have to do that as well as build new cells,” Vander Heiden said in the release.

This discovery is what led the researchers to see that cancerous growth could be turned off by boosting pyruvate kinase activity.

The researchers wanted to see if they were able to achieve a similar finding in a previous study that saw increasing PKM1 activity restores cancer cells to a normal metabolic state, but this time with PKM2.

They tested two of the compounds in cancer cells grown in the lab, and one in mice implanted with human tumors. They found that in the mice, the tumors did not grow.

“It seems to move cells away from a program where they can build stuff, to a program where they just make ATP", Vander Heiden said in the release.

The team is now trying to figure out what happens inside a cell when PKM2 is made into an active form. They are developing mouse models to determine whether activating this enzyme shrinks tumors that have already been established in mice.