Many clinical trials have looked to the use of metformin - a drug already used to treat diabetes - as a way of suppressing tumor growth in cancer by activating a molecule called AMP-activated protein kinase. But new research suggests that activation of this molecule may actually encourage tumor growth.
The study findings are published in the journal Proceedings of the National Academy of Sciences.
However, the research team, led by Dr. Biplab Dasgupta of the Division of Hermatology/Oncology at Cincinnati Children's Hospital Medical Center, says their study shows metformin can stop tumor growth, but through a process independent of AMP-activated protein kinase (AMPK) activation.
They add that their findings suggest that clinicians testing metformin for cancer treatment should "consider a careful re-evaluation of their clinical data."
AMPK is a metabolic enzyme that plays a part in determining energy levels in cells. According to the researchers, the enzyme controls many metabolic pathways that assist cells in regulating energy usage and survival when exposed to physiological stress.
The investigators explain that cancer cells adjust their metabolism so they can continue to live and grow in stressful environments.
Some studies have found that activation of AMPK using metformin may stop tumor growth, while others have suggested otherwise.
Metformin 'blocks mTOR activity' to kill cancer cells
In an attempt to reach a conclusion, the investigators conducted experiments using human glioblastoma (brain cancer) cells and tumor cells that had been transplanted in mice.
On comparing healthy human and mouse brain tissue with tissue containing glioblastoma cells, the researchers found that AMPK activation was already high - suggesting that the way metformin reduces cancer growth may not involve AMPK at all.
They then treated the human glioblastoma cells with metformin. From this, they found the drug blocked tumor growth by inhibiting the mammalian target of rapamycin (mTOR) pathway. This is a molecule that has been associated with many cancers.
The researchers then tested a compound called A769662 - a compound that directly binds to AMPK - on the glioblastoma cells. This treatment did not kill any glioblastoma cells, further suggesting that AMPK activation is not involved in stopping tumor growth.
Commenting on the research, Dr. Dasgupta says:
"Our findings do not suggest that clinical trials using metformin should be stopped. Metformin appears to be a very useful drug, but the drug's mechanism of cancer suppression is not clear.
However, our findings unveil a potential role for AMPK as a tumor growth supporter, not a suppressor, in the type of cancer that we study. This is why clinicians using metformin in clinical trials should use caution during data interpretation."
Dr. Dasgupta adds that the research team is already analyzing how human glioblastoma cells are impacted by specific genetic inhibition of AMPK. He notes that this research is not yet finished, but early results suggest that blocking AMPK activity may kill glioblastoma cells.
Earlier this year, Medical News Today reported on a study suggesting that metformin may also have anti-aging properties.