Image courtesy of PNAS
A diabetes medication and an antihypertensive drug may prove effective in the treatment of hematologic malignancies and other cancers, according to preclinical research published in Science Advances.
Past research has shown that metformin, a drug used to treat type 2 diabetes, has anticancer properties.
However, the usual therapeutic dose is too low to effectively fight cancer, and higher doses of metformin could be too toxic.
With the current study, researchers found that the antihypertensive drug syrosingopine enhances the anticancer efficacy of metformin without harming normal blood cells.
The team screened over a thousand drugs to find one that could boost metformin’s efficacy against cancers.
They identified syrosingopine and tested it in combination with metformin—at concentrations substantially below the drugs’ therapeutic thresholds—on a range of cancer cell lines and in mouse models of liver cancer.
Thirty-five of the 43 cell lines tested were susceptible to both syrosingopine and metformin. This included leukemia, lymphoma, and multiple myeloma cell lines.
In addition, the mice given a short course of syrosingopine and metformin experienced a reduction in the number of visible liver tumors.
The researchers also tested syrosingopine and metformin in peripheral blasts from 12 patients with acute myeloid leukemia and a patient with blast crisis chronic myeloid leukemia. All 13 samples responded to the treatment.
On the other hand, syrosingopine and metformin did not affect peripheral blood cells from healthy subjects.
“[A]lmost all tumor cells were killed by this cocktail and at doses that are actually not toxic to normal cells,” said study author Don Benjamin, of the University of Basel in Switzerland.
“And the effect was exclusively confined to cancer cells, as the blood cells from healthy donors were insensitive to the treatment.”
The researchers believe metformin functions by lowering blood glucose levels for cancer cells, starving them of essential nutrients needed for their survival. However, it is not clear how syrosingopine works in conjunction with metformin.
The team emphasized the need for more research evaluating the drugs in combination.
“We have been able to show that the 2 known drugs lead to more profound effects on cancer cell proliferation than each drug alone,” Dr Benjamin said. “The data from this study support the development of combination approaches for the treatment of cancer patients.”
