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Stories of Impact

AICR Spotlight Research: Paul Spagnuolo, PhD

Avocados target leukemia cells – How an avocado or two could rewire and destroy leukemia cells

With a background in food science and drug delivery, AICR grantee Paul Spagnuolo is intrigued by what’s in our foods that not only taste great but also hold cancer-fighting potential. Recently he’s focused on avocados as a weapon against leukemia.

Guacamole is an easy and favorite appetizer. The perfectly shaped avocado holds more than just its soft fruit, it has a cancer-fighting property called a nutraceutical that provides an extra health benefit beyond nutrition. Let’s break this down.

So called superfoods are all the rage these days; those fruits, vegetables, and nuts that are nutrient-dense, satisfying and healthy. Avocados are on that list. Do these foods live up to the hype? The AICR puts these kinds of healthy claims to the test through grants like the Young Investigator Award for Outstanding Research.  Its recipient, Paul Spagnuolo, Ph.D., grew up in Italian culture, with a love for Mediterranean food, including avocados.

At the University of Guelph in Canada, Dr. Spagnuolo and his team are exploring the role of nutrition in acute myeloid leukemia (AML), a type of blood cancer that affects both children and adults. Treatments for this condition have changed little in over 40 years. It’s complicated by the fact that for nearly half of these patients, cancer returns – which requires additional treatment.

It appears that in lab studies, a compound found in avocados targets and destroys lurking leukemia cells. And there’s a bonus. This same compound seems to inhibit cellular processes linked to obesity and diabetes. Avocados are in a food category of nutraceuticals that can impact health. More on that in a moment.

It’s still early in Spagnuolo’s research, but his findings are part of a larger body of work he’s developed that identifies and screens the health effects of food compounds. His approach to nutrition is similar to drug development and provides evidence of the powerful role of foods to lower the risk of cancer, and other diseases.

Congratulations on receiving the Young Investigator Award for Outstanding Research!

Thanks, that was exciting and I’m still smiling! My team works very hard and it is deeply satisfying when we are recognized for our efforts.

Q: You earned a post-doc in drug discovery; what led to your interest in food-related research?

A: I received a master’s degree in food science. I have always loved food – and was most interested when I started out studying food, in understanding its chemistry. Then I completed a Ph.D. in looking at how consuming large amounts of food bioactive – food compounds that have a biological effect or nutraceuticals– interact with health. From there I was interested in seeing how nutraceuticals could be used as drugs.

Q: Can you explain your approach to nutraceuticals as therapeutics?

A: I went to the University in Toronto where they have a major cancer center and where I worked on identifying novel therapeutics in cancer and drug discovery and learned, from one of the very best, how to identify drugs to treat disease. When I left I started my own independent research group at the University of Waterloo [in Ontario], I married this unique food science background to drug discovery. When you do drug screens, there are systems in place. When I started my own lab, I made a drug library that consisted of only nutraceutical compounds. I don’t think this exists anywhere else in the world. These food compounds are bioactive so by definition, these molecules have biological activity. If they have biological activity, the question is: how can we use them to treat disease?

Q: The compound you are focusing on now for AML is avocatin B, a naturally occurring nutraceutical, that comes from the avocado. Did your research here start by researching the avocado or another way?

A: We didn’t start out by saying, what molecule in the avocado is the best. We actually tested hundreds of food-derived molecules by asking: which of these is best at killing cancer cells? We use a systematic method and do a robust screen with cell-based experiments. When I started this about 800 molecules from different foods were tested to see what kills the AML cells: The best at that was the avocatin B compound. We’ve published studies on several molecules and the most interesting one is the avocado molecule. We found it imparts the greatest [biological] activity across multiple models. Our research in avocatin B has seen effects in diet-induced obesity and improving glucose response.

Q: What was the next step after you identified avocatin B?

A: From there we went out to validate selective toxicity. The goal is to selectively kill the cancer cells, without harming the normal cells.

Q: In general, how does the compound do this?

A: It changes the way cells use fat for energy and that kills the leukemia cell. Over the last decade, we‘ve come to understand that cancer cells are rewired. In 2015, we published a paper showing the molecule accumulates inside the mitochondria – [the energy-producing part of the cell] and we have recently published a paper showing how the molecule disrupts the fatty acid process the leukemia cell needs. When you’re building houses, you need bricks. For leukemia cells, they use fatty acid oxidation, breaking down fats to create those bricks. So by depriving the leukemia cells of those essential building blocks you stop it from growing and creating more cells or – using the analogy – building those houses. In normal cells, if you shut this pathway down, these cells are able to use other substances to make those bricks. But not leukemia cells.

Q: Your AICR study uses a powdered form of avocados in your study. Tell us more.

A: For the AICR study, we created a diet that is fortified with avocatin B. It’s similar to an avocado powder that we used in a human clinical trial but this study used mice and was equivalent to a person eating two avocados a day. What we are asking is, if we fortify a diet with this avocatin B molecule, is there a way we can delay or reduce a patient from relapsing? With COVID, we’re behind schedule, but we’re close to completing the study.

Q: How do you see this study helping move the research forward?

A: It’s all part of my research program: the more we understand the mechanisms through which nutraceuticals like avocado bioactives (i.e., avocatin B) get in key tissues and function in the body, the better we can execute this important work and ultimately, improve patient outcome.

Q: Your conclusion is that eating just one avocado a day could kill the cancer cells and help prevent a relapse. How does this relate to AICR?

A: That’s why I love AICR – they spend their time on this field of diet and cancer where few agencies do. These kinds of studies get airplay in the media but not as much in scientific circles where we really need them.

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