AMPK Activation Leads to Cancer Growth & Not Inhibition

Many clinical studies have looked towards the use of- a drug currently used to deal with diabetes – as a way of controlling tumor growth in cancer by initiating a molecule known as AMP-activated protein kinase. But new study indicates that activation of this molecule may basically motivate tumor development.

The research results are released in the journal Proceedings of the National Academy of Sciences. On the other hand, the study team, guided by Dr. Biplab Dasgupta of the Division of Hermatology/Oncology at Cincinnati Children’s Hospital Medical Center, states that their research shows metformin can stop tumor development, but via a process known as independent of AMP-activated protein kinase (AMPK) activation. They add that their results recommend that physicians examining metformin for cancer therapy should “think about a careful re-evaluation of their clinical data.”

AMPK is a metabolic enzyme that performs a part in identifying energy levels in cells. In accordance to the scientists, the enzyme manages many metabolic pathways that support cells in controlling energy usage and survival when subjected to physiological stress.

The researchers describe that cancer cells modify their metabolism so they can proceed to live and grow in stressful surroundings. Some researches have identified that activation of AMPK using metformin may end tumor development, while others have recommended otherwise.

Metformin ‘blocks mTOR activity’ to eliminate cancer cells
In an effort to reach a summary, the researchers performed tests using human glioblastoma (brain cancer) cells and tumor cells that had been transplanted in mice. On evaluating healthy human and mouse brain tissue with tissue that contains glioblastoma cells, the scientists identified that AMPK activation was previously high – indicating that the way metformin decreases cancer development may not include AMPK at all.

They then handled the human glioblastoma cells with metformin. From this, they identified the drug obstructed tumor development by suppressing the mammalian target of rapamycin (mTOR) pathway. This is a molecule that has been related with many cancers.

The scientists then examined a substance known as A769662 – a compound that directly binds to AMPK – on the glioblastoma cells. This therapy did not destroy any glioblastoma cells, further indicating that AMPK activation is not engaged in stopping tumor development.

Commenting on the study, Dr. Dasgupta states that:
“Our results do not recommend that clinical studies using metformin should be ceased. Metformin seems to be to be a really helpful drug, but it’s mechanism of cancer withdrawal is not clear.

However, our results reveal a potential role for AMPK as a tumor growth promoter, not an inhibitor, in the type of cancer that we research. This is why clinicians using Metformin in clinical studies that should use caution while in data interpretation.” Dr. Dasgupta adds that the study group is presently analyzing how human glioblastoma cells are affected by particular genetic inhibition of AMPK. He notes that this study is not yet completed, but early outcomes recommend that blocking AMPK activity may kill glioblastoma cells.