Researchers from the LSU School of medicine have recently found that metformin, a common diabetes treatment, may be effective in combatting cancer. The team found that the Type 2 diabetes drug could provide unique benefits to those with cancers that lack the Nischarin protein, often seen in breast cancer. This work was led by Suresh Alahari, PhD, Professor of Biochemistry and Genetics at LSU Health New Orleans School of Medicine and was published online in the International Journal of Cancer on September 16.
Nischarin, a protein molecule involved in tumor suppression and other biological processes, was discovered by Alahari. His research into this protein has been used largely in breast cancer, being that Nischarin expression is frequently reduced in this form of cancer. In this latest study, however, Alahari and colleagues showed that interfering with Nischarin expression can delay the development of the mammary gland, increase tumor growth and metastasis, and reduce the activation of AMPK.
The AMPK enzyme plays a pivotal role in metabolism and is thought to be therapeutic for metabolic diseases and potentially cancer. The full mechanism by which metformin acts is still unknown, but researchers have identified that the drug works in part by activating AMPK.
“The clinical documentation that diabetic patients on a metformin regimen display reduced risks of developing cancer poses the tantalizing possibility that this approach to treating cancer might prove to be an effective and unrealized therapeutic opportunity,” explained Alahari.
In their work, Alahari and colleagues showed that metformin successfully activates AMPK and inhibits tumor growth in malignancies that lack Nischarin. These findings indicate that metformin could serve as a powerful therapeutic agent in treating these unique tumors.
“We found that Nischarin-deleted tumor cells had lower AMPK activity than Nischarin-positive cells,” said Alahari. He continued to explain that “metformin treatment activated AMPK more efficiently in Nischarin-deleted mice, and metformin suppressed tumor growth of Nischarin-deleted mice. Collectively, our data suggest that Nischarin disruption promotes breast tumor development, AMPK signaling is important for Nischarin-mediated suppression of breast tumors, and activation of AMPK by metformin suppresses breast tumor growth in Nischarin-lacking mice.”
Breast cancer often displays reduced expression of Nischarin, particularly in triple-negative breast cancers. Impacting 2.1 million women every year, breast cancer is the most commonly occurring cancer among women as per the World Health Organization. Being that this disease accounts for roughly 15% of all cancer deaths among women, finding effective treatments is of paramount importance. With these new findings regarding metformin’s ability to combat Nischarin-lacking cancer, Alaharin and colleagues have made a breakthrough in the treatment of breast cancer and other tumors.
“The discovery that the effectiveness of certain drugs, such as metformin, are influenced by the level of Nischarin expression could help identify specific patients in whom it is most likely to prove beneficial,” added Alahari. “In this way, Nischarin expression could serve as a biomarker to help inform decisions in management by identifying a subset of patients most likely to benefit from AMPK activator therapies.”
In this work, Alahari was joined by LSU researchers Shengli Dong, Rajamani Rathinam, Steven Eastlack, Mazvita Maziveyi, and Bernardo Ruiz-Calderon. Their research was backed by funding from both LSU Health New Orleans and the Fred G. Brazda Foundation.
Knockout model reveals the role of Nischarin in mammary gland development breast tumorigenesis and response to metformin treatment.: Previously our lab discovered the protein Nischarin and uncovered its role in regulating cell migration and invasion via… https://t.co/EIhGv20eHb
— Breast Cancer News (@BreastCancerBio) September 17, 2019