Drug combination more effective on cancer cell proliferation.
A combination of drugs used to treat diabetes and hypertension may effectively combat cancer.
Although the type 2 diabetes drug metformin has demonstrated anti-cancer properties, the usual therapeutic dose is too low to treat cancer.
In a study published in Science Advances, investigators found that the antihypertensive drug syrosingopine potentiates the anti-cancer efficacy of metformin. Meaning, the drug combination drives cancer cells to programmed suicide.
Higher doses of metformin can inhibit the growth of cancer cells, but can also induce unwanted adverse events. For the study, the investigators screened more than 1000 drugs to determine whether they could enhance the anti-cancer action of metformin, before selecting syrosingopine.
“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,” said first study author Don Benjamin. “And the effect was exclusively confined to cancer cells, as the blood cells from health donors were insensitive to the treatment.”
The investigators conducted an experiment in mice with malignant liver cancer who were administered the combination therapy. The results of the study showed that enlargement of the liver was reduced, and the number of tumor nodules either lowered or completely disappeared.
Metformin, which reduces blood glucose levels, can block the respiratory chain in mitochondria, and syrosingopine inhibits the degradation of glucose. When the drug combination is used, it interrupts the viral processes that provides the cell with energy. Since cancer cells have a high energy consumption, it makes them extremely vulnerable when the energy supply is reduced, according to the study.
The investigators tested a variety of other compounds with the same mode of action to demonstrate that the inhibition of the respiratory chain in the mitochondria is a key mechanism.
“We have been able to show that the 2 known drugs lead to more profound effects on cancer cell proliferation than each drug along,” Benjamin said. “The data from this study support the development of combination approaches for the treatment of cancer patients.”