A University of Rochester team has uncovered how tumors tap the antioxidant glutathione as a powerful fuel source. The discovery could guide new drugs and diet-based strategies to starve cancer cells while sparing healthy tissue.
Cancer cells may be far more resourceful eaters than scientists realized — and a common antioxidant is on the menu.
Researchers from the University of Rochester’s Wilmot Cancer Institute have discovered that tumors can tap the antioxidant glutathione as a potent fuel source, and that blocking this process can slow cancer growth in preclinical models. The work, published in the journal Nature, opens a new path for therapies that aim to starve tumors without harming healthy cells.
Glutathione is a substance the body makes naturally to help protect cells from damage. It is also widely sold as a dietary supplement and often marketed as a health booster. But in the harsh, nutrient-poor environment around a tumor, glutathione appears to play a very different role.
Lead researcher Isaac Harris and his team found that cancer cells are effectively “addicted to” glutathione. They showed that tumors can break down this antioxidant and use its components as fuel, giving them a survival edge when other nutrients are scarce.
Harris, an associate professor in the Department of Biomedical Genetics, and a member of Wilmot’s Genetics, Epigenetics, and Metabolism research program, noted the findings highlight a key difference between cancer cells and healthy cells.
“Cancer cells and normal cells potentially use different food sources,” he said in a news release, “and we discovered how cancer cells, specifically, break down this antioxidant and use it as fuel.”
For decades, most glutathione research has focused on its protective role in preventing or repairing cell damage. The Rochester team’s work suggests that in cancer, glutathione can also act as a pro-tumor nutrient.
Harris emphasized that this calls for a broader rethink of how scientists view the tumor “pantry” — the mix of nutrients that cancer cells draw on to grow and spread.
“Maybe we need to re-examine the pantry that cancer relies on and look at things that we never thought could actually be used as food for tumors,” he said. “There are additional complex metabolites that others are looking at, so we’re potentially opening a whole new interest into how cancer cells acquire nutrients and how to block that activity. It’s a really exciting time.”
To probe glutathione’s role, the team analyzed breast tumor samples donated to Wilmot’s Biobank. By isolating and studying the fluid inside these tumors, they found that glutathione was stored there in large amounts, suggesting that cancer cells were actively consuming it as a nutrient source.
Using preclinical models of breast cancer, the researchers then tested what would happen if they blocked tumors’ ability to use glutathione. When they interfered with this process, tumor growth slowed, supporting the idea that glutathione is a critical fuel for cancer cells.
Early evidence suggests this strategy may not be limited to breast cancer. Harris said preliminary data indicate that many types of tumors consume glutathione, raising the possibility of a broader treatment approach.
The new study builds on earlier work from the Rochester group and their colleagues that explored how diet and other antioxidants intersect with cancer. In previous research, Harris’ team, working with Tom Campbell and Erin Campbell showed that a whole-food, plant-based diet may reduce certain pro-tumor food sources in the body. Another Wilmot scientist, Jeevisha Bajaj, reported that taurine, an antioxidant found in foods, supplements and energy drinks, can drive leukemia cell growth.
Together, these findings point to a complex relationship between antioxidants, nutrition and cancer biology. Substances that may be helpful or neutral in some settings can be hijacked by tumors in others.
“It’s important to understand how cancer hijacks certain substances that we may think of as harmless,” Harris said, noting that antioxidants can act as a double-edged sword.
That does not mean people should avoid fruits and vegetables, he emphasized. Whole foods contain a mix of nutrients and fiber that support overall health and may help lower cancer risk through multiple pathways, including weight control and reduced inflammation.
“Eating a balanced diet with fruits and vegetables is important. It can control weight, reduce inflammation, and support a healthy immune system,” Harris said.
The concern, he explained, is with high-dose, unregulated supplements that deliver large amounts of a single compound, such as glutathione, directly into the body.
“But people should be cautious about taking supplements in general, particularly glutathione. Taking a pill that is unregulated by the FDA and has a high concentration of glutathione can present risks,” Harris added.
In the lab, Harris’ group used advanced screening technologies to search for compounds that could block tumors from using glutathione. They identified a promising drug that had been developed nearly a decade ago, and are now working to refine and improve it.
University of Rochester chemist Tom Drive, the Robert K. Boeckman Jr., and Mary H. Delton Family Distinguished Professor in Organic Chemistry, and cancer metabolism expert Joshua Munger, a professor of biochemistry and biophysics, are collaborating to better understand how this drug works, which proteins it targets, and how it might be optimized to cut off glutathione-based fuel lines to tumors.
Future plans include testing combinations of anti-cancer drugs alongside dietary changes that could further limit the nutrients tumors depend on. The long-term goal is to design treatments that precisely target cancer cells’ unique appetites while sparing normal tissue.
“Even though glutathione was discovered 100 years ago, we are finding completely new aspects to its biology,” Harris concluded. “There is a lot left to understand but we’re hopeful we can translate these discoveries to new therapies.”
If successful, this line of research could help usher in a new generation of cancer treatments that do not just attack tumors directly, but also quietly starve them by cutting off their hidden food sources.