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Published in CenterView on April 01, 2013
Levenson
Levenson

UMMC researchers unlock pterostilbene’s ability to suppress cancer growth

By Jack Mazurak

A compound in blueberries – pterostilbene – helps keep prostate cancer tumors from growing and spreading in mice, researchers at the University of Mississippi Medical Center reported in a paper published last month.

A mouthful of a name for coming in such small fruit, pterostilbene – pronounced tero-STILL-bean – also inhibits tumor growth and prevents metastasis better than resveratrol, a compound found in grapes and red wine.

It’s too early to say wholesale quaffing of blueberries could cure prostate cancer in men, but the findings suggest more research might yield a promising cancer treatment, said Dr. Anait S. Levenson, associate professor of pathology and a researcher at the UMMC Cancer Institute.

“These experiments involved multiple disciplines to look at what we eat, not just as nutrition, but as medicine,” said Levenson, the study’s principal investigator and lead author on the paper.

Prostate cancer, second only to non-melanoma skin cancer, is the most common cancer among men in the U.S. and one of the leading causes of cancer death among men. Scientists working with natural compounds like pterostilbene and resveratrol hope they may fight cancer with fewer side effects than chemotherapy and radiation.

In her research, Levenson tested resveratrol, pterostilbene and five other stilbene compounds – each with slightly different molecular structures – on highly aggressive strains of prostate cancer.

“I knew that you could synthesize stilbene analogues, but I couldn’t do it myself,” she said. “I needed a chemist.”

Rimando
Rimando

In Oxford, she found and collaborated with Agnes M. Rimando, research chemist with the USDA Agricultural Research Service Natural Products Utilization Research Unit housed at the University of Mississippi’s National Center for Natural Products Research.

Of all the compounds, pterostilbene did the best at inhibiting MTA1, a protein associated with prostate cancer’s aggressiveness. Both compounds also helped rescue the tumor suppressor protein p53.

With those results in hand, Levenson and scientists in her lab grew human prostate cancer tumors in prostates of genetically immunocompromised mice. Researchers then treated the mice daily with 50 mg/kg of resveratrol or pterostilbene over eight weeks.

Tumors in a control, untreated group grew and highly metastasized. The mice treated with resveratrol grew considerably smaller tumors. But those treated with pterostilbene grew even smaller tumors and developed significantly less metastasis.

On March 1, the Public Library of Science One published her paper, “Pterostilbene Acts through Metastasis-Associated Protein 1 to Inhibit Tumor Growth, Progression and Metastasis in Prostate Cancer.”

Why pterostilbene? Simple, Levenson said. Prior research had shown anti-cancer properties of both resveratrol and pterostilbene. But resveratrol has low bioavailability, meaning it’s hard to find in any great quantity in its natural form and is eliminated from the body quicker, Levenson said.

Dr. Lucio Miele, UMMC Cancer Institute director, said Levenson’s findings and collaboration with the USDA, Ole Miss and the Natural Products Center make the work stand out as exemplary.

“This type of collaborative, interdisciplinary research is the kind that we encourage at the Cancer Institute,” he said. “Development of novel natural products could lead to improved cancer treatments and chemopreventive strategies and help reduce human suffering.”

Two intramural grants from UMMC funded the research. Levenson received a $561,000 Idea Development Grant in January from the Department of Defense to continue her work.

Next, Levenson wants to study the efficacy of pterostilbene in humans and how well various combinations of pterostilbene and chemotherapeutic drugs work in treating cancer.

“Can we use pterostilbene as chemopreventive and therapeutic nutraceutical to fight prostate cancer in men? Is there a synergistic effect? Can you cut down on the dose of chemotherapeutics so that the side effects are less?” Levenson asked.

“Those are questions I would like my lab to answer.”