Diabetes, hypertension medication found to be effective against cancer cells
A team of researchers at the Biozentrum of the University of Basel in Switzerland has found that a combination of a diabetes drug and an antihypertensive medication is effective in fighting cancer cells.
The most widely prescribed drug for the treatment of type 2 diabetes, metformin, also displays anti-cancer properties aside from its blood sugar lowering effect. However, the usual therapeutic dose is too low to effectively combat cancer.
But the research team, led by Professor Michael Hall, discovered that the antihypertensive drug syrosingopine increases the anti-cancer efficacy of metformin. Apparently, this drug combination drives cancer cells to programmed “suicide”.
At higher doses, the antidiabetic drug inhibits the growth of cancer cells but could also induce unwanted side effects. Therefore, the researchers screened over a thousand drugs for whether they can enhance the anticancer action of metformin.
A favorite emerged from this screening: syrosingopine, an antihypertensive drug. As the study shows, the cocktail of these two drugs is effective in a wide range of cancers.
According to the study’s first author, Don Benjamin, the drug combination was able to kill almost all tumor cells in samples collected from leukemia patients at doses that are actually not toxic to normal cells. The effect was also exclusively confined to cancer cells as the blood cells of healthy donors were insensitive to the treatment, he said.
In mice with malignant liver cancer, enlargement of the liver was reduced after the therapy. Also the number of tumor nodules was less and in some animals the tumors disappeared completely.
A glance at the molecular processes in the tumor cells explains the drug combination’s efficacy: metformin lowers not only the blood glucose level, but also blocks the respiratory chain in the energy factories of the cell, the mitochondria. The antihypertensive drug 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.
By testing a range of other compounds with the same mode of action, the scientists could demonstrate 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.
“We have been able to show that the two known drugs lead to more profound effects on cancer cell proliferation than each drug alone,” explains Benjamin. “The data from this study support the development of combination approaches for the treatment of cancer patients.”
This study may have implications for future clinical application of combination scenarios targeting the energy needs of tumor cells.
