Researchers at Washington State University have identified a fatty acid that can kill cancer cells. The experts demonstrated that dihomo-gamma-linolenic acid (DGLA) triggers a type of cell death known as ferroptosis in actual human cancer cells.
Ferroptosis is a recently discovered cell death pattern that is dependent on iron. This mode of cell death has become an important focus for medical research because it is associated with many serious illnesses, including cancer and cardiovascular, neurodegenerative, and hepatic diseases.
The discovery that DLGA induces ferroptosis has many implications, including a step toward a potential treatment for cancer, said study co-author Professor Jennifer Watts.
“If you could deliver DGLA precisely to a cancer cell, it could promote ferroptosis and lead to tumor cell death,” said Professor Watts. “Also, just knowing that this fat promotes ferroptosis might also affect how we think about conditions such as kidney disease and neurodegeneration where we want to prevent this type of cell death.”
DGLA is a polyunsaturated fatty acid that is found in small amounts in the human body, yet rarely found in the human diet. For nearly 20 years, Professor Watts has been researching DGLA and other dietary fats using the microscopic worm C. elegans as an animal model.
In previous work, Professor Watts and her team discovered that feeding nematodes a diet of DGLA-containing bacteria killed all of their germ cells, as well as the stem cells that make the germ cells. This cell death pattern resembled ferroptosis.
“Many of the mechanisms we saw in the nematodes were consistent with the hallmarks of ferroptosis in mammalian systems, including the presence of redox-active iron and the inability to repair oxidized lipids, which are like molecular executioners,” explained study first author Marcos Perez.
To investigate further, the researchers collaborated with Scott Dixon of Stanford University, who studies ferroptosis and its potential for fighting cancer.
The team showed that DGLA could induce ferroptosis in human cancer cells. In addition, the experts found another fatty acid, an ether lipid, that worked against DGLA. When they took out the ether lipids, the cells exposed to DLGA died faster.
Professor Watts and her team recently received a $1.4 million grant from the National Institutes of Health to investigate what makes the nematode germ cells so susceptible to DGLA. The researchers will also explore the role of mitochondria in ferroptosis.
The study is published in the journal Developmental Cell.