Combination of diabetes drug and antihypertensive agent kills cancer cells

Combination of diabetes drug and antihypertensive agent kills cancer cells

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Deadly combination: drug cocktail turns cancer cells off the juice

Researchers have found that a commonly used diabetes medication in combination with a hypertension medication inhibits cancer growth. This drug cocktail also cuts the energy supply to cancer cells and kills them as a result.

More and more cancers

Health experts say that more and more people are getting cancer. According to the World Cancer Report of the International Agency for Research on Cancer (IARC), 20 million new cases of cancer could occur worldwide by 2025. In Germany, the number of new diagnoses has almost doubled since 1970. However, more and more people survive cancer today. This also has to do with the fact that new insights are constantly being gained on how cancer can be treated. Researchers are currently reporting on a study that showed that a certain drug cocktail can kill cancer cells.

Energy supply to cancer cells is cut

The often prescribed diabetes medicine metformin not only lowers blood sugar levels, but also works against Parkinson's, as researchers from Tübingen reported last year.

It also has an anti-cancer effect. However, the current dose for the treatment of diabetes is too low to slow cancer growth, reports the University of Basel in a communication.

However, researchers led by Prof. Michael Hall at the Biozentrum of the University of Basel were able to show in an older study that the antihypertensive drug syrosingopin increases the cancer-inhibiting effects of metformin.

In a follow-up study, which was recently published in the specialist magazine "Cell Reports", the scientists are now reporting that this drug cocktail cuts the energy supply to cancer cells.

The resulting lack of energy ultimately drives the cancer cells into "suicide".

Particularly high energy requirements

As the experts explain, cancer cells have a particularly high energy requirement due to their increased metabolism and rapid growth.

A limiting factor is the molecule NAD +, which plays a central role in the conversion of nutrients into energy.

"In order to keep the energy-producing machinery running, NAD + must be continuously manufactured from NADH," explains Don Benjamin, first author of the study.

"Interestingly, both metformin and syrosingopin prevent the regeneration of NAD +, but in two very different ways."

Effectiveness under the microscope

Many tumor cells shift their metabolism towards sugar burning, which means that they gain their energy primarily from the breakdown of glucose to lactate.

However, if lactate accumulates in the cell, this pathway is paralyzed. That is why the cancer cells use specific lactate transporters to channel it out of the cell.

"We have now found that syrosingopine switches off the two most important transporters and thus prevents the export of lactate from the cell," said Benjamin.

"A high lactate concentration in the cell in turn stops the recycling of NAD +."

Deadly combination

According to the scientists, the antidiabetic drug metformin blocks the second way of regenerating NAD +.

Therefore, the combined treatment with the antihypertensive agent leads to a complete loss of NAD + recycling capacity.

The NAD + deficiency ultimately kills the cell because it can no longer produce enough energy.

The inhibition of lactate transporters by syrosingopin or other drugs with a similar effect improves the anti-cancer effects of metformin and thus appears to be a promising approach to combating cancer, according to the scientists. (ad)

Author and source information

Video: Drug DiscoveryMedicinal Chemistry at UCLA: Xtandi and Others (July 2022).


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