26 April 2019

A drug abandoned as a treatment for diabetes may protect against the development of T-cell lymphoma, researchers from University of Dundee have reported.

The mouse study, published in the journal Cell Reports, focussed on a protein AMPK, which was thought to confer protection against the disease. Two diabetes drugs, metformin and phenformin, activate AMPK, but phenformin was abandoned in many countries 30 years ago, after it was discovered that it caused lactic acidosis, a rare but potentially fatal side-effect.

The study confirmed that AMPK played a key role in protecting against lymphoma development, the researchers said. However, the researchers found that phenformin was able to penetrate the diseased cells, whereas metformin was not.

Previous studies have linked metformin to protection against cancer. Researcher Professor Grahame Hardie said: “We now think that the apparent protective effect of metformin in humans was due to activation of AMPK not in the cancer cells themselves, but elsewhere in the body, which protects against cancer indirectly by lowering insulin levels.

“On the other hand, the protective effect of phenformin is due to activation of AMPK within the cells that give rise to the cancer, a mechanism that is likely to be applicable to other forms of cancer.”

He added: “If our findings can be applied to humans, individuals at high risk of developing cancer might be treated with phenformin.

“The small risk of lactic acidosis caused phenformin to be dropped for use in diabetes - but may be more acceptable if it was used as an anti-cancer agent.”

Source: Vara-Ciruelos, D., Dandapani, M., Russell, F.M., Grzes, K.M., Atrih, A., Foretz, M., Viollet, B., Lamont, D.J., Cantrell, D.A., & Hardie, D.G. (2019) “Phenformin, But Not Metformin, Delays Development of T Cell Acute Lymphoblastic Leukemia/Lymphoma via Cell-Autonomous AMPK Activation”, available from doi: 10.1016/j.celrep.2019.03.067


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