Metformin And This Drug Starve Cancer Cells

Researchers have found a potential anti-cancer therapy, and its key ingredient is metformin.

Cancer tumors need energy to grow—a lot of it. But researchers at the University of Basel in Switzerland found that metformin, when combined with the blood pressure drug syrosingopine, cuts off a cancer tumor’s energy supply so that its cells starve and die.

Here’s how it works:

Cancer cells primarily use the anaerobic glycolysis energy pathway to produce ATP molecules they can use for energy. Other cells in the human body use a combination of the three energy-producing pathways: anaerobic glycolysis, aerobic glycolysis, and the phosphagen system. The anaerobic glycolysis system produces a lot of energy, which cancer cells need, but it also produces lactate.

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The molecule NAD+ is a key part of anaerobic glycolysis as it helps turn glucose into ATP. To keep the supply of energy going, NAD+ must be constantly regenerated from another molecule, NADH. Metformin and syrosingopine work together to block the regeneration of NAD+ using two different strategies, thus cutting off a cancer tumor’s energy source.

Syrosingopine blocks lactate transporters. If the lactate created by anaerobic glycolysis cannot be removed, high lactate concentration will prevent NAD+ from being produced from NADH. But there are two ways that NAD+ can regenerate. Syrosingopine blocks the first, and metformin blocks the second. Without a way to create energy to fuel their growth, cancer cells will die.

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Separately, the two drugs stick to doing their own jobs, but together, they could be an effective anti-cancer therapy.

Metformin is common drug prescribed to treat type 2 diabetes and helps lower blood sugar by keeping the liver from making too much glucose and by increasing the body’s insulin sensitivity (encouraging glucose uptake into the cells).

This isn’t the first time that metformin has been suspected of benefits beyond blood sugar control, like protecting against vision loss or even increasing longevity. It would be quite the feather in its cap if metformin proved an effective cancer treatment along with its blood-pressure-lowering sidekick, syrosingopine.

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The research is in its beginning stages, but the authors of the study, first published in the journal Cell Reports in December 2018, are hopeful that their discovery could lead to an effective cancer treatment.

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