Cancer researchers: Cells respond to drug combination

A team of cancer researchers at the Biozentrum of the University of Basel in Switzerland has published in Science Advances that specific cancer cells respond to a combination of a diabetes medication and an antihypertensive drug.

At higher doses, the antidiabetic drug Metformin, the most widely prescribed drug for the treatment of Type 2 diabetes, inhibits the growth of cancer cells — but also could induce unwanted side effects. The researchers screened more than 1,000 drugs to determine if they can enhance the anticancer action of Metformin. The screening led to Syrosingopine, an antihypertensive drug.

“We have been able to show that the two known drugs lead to more profound effects on cancer cell proliferation than each drug alone,” said Don Benjamin, the paper's author. “The data from this study support the development of combination approaches for the treatment of cancer patients.”

In mice with malignant liver cancer, enlargement of the liver was reduced after the therapy. Also, the number of tumor nodules was less — in some animals, the tumors disappeared completely. Metformin lowers the blood glucoseA type of sugar; the chief source of energy for living organisms. level and also blocks the respiratory chain in the cell mitochondria. Syrosingopine inhibits, among other things, the degradation of sugars.

Thus, the drugs interrupt the vital processes which provide energy for the cell. Due to their increased metabolic activity and rapid growth, cancer cells have a particularly high energy consumption, which makes them extremely vulnerable when the energy supply is reduced.

“For example, in samples from leukemia patients, we demonstrated that almost all tumor cells were killed by this cocktail and at doses that are actually not toxic to normal cells,” Benjamin said. “And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment.”

The scientists showed that the inhibition of the respiratory chain in the mitochondria is a key mechanism. These also reduced cancer cell growth in combination with the antihypertensive drug.

• Syrosingopine sensitizes cancer cells to killing by metformin