In the study published online May 8 in the Oxford Journals’ Carcinogenesis and led by Bal L. Lokeshwar, Ph.D., professor of urology and radiation oncology and Co-Director of Research in the Department of Urology, researchers demonstrated that Ericifolin, a complex compound in the allspice berry, significantly slows the growth of prostate cancer tumors by suppressing the androgen receptor (AR). A molecule central to the growth and metastasis of prostate cancer, AR enables prostate cancer cells to survive even after hormone therapy, which along with surgery and radiation is the standard treatment for prostate cancer.
“Androgen receptor, or AR for short, is the principal drug target for the treatment of prostate cancer, but there is no drug that completely eliminates AR. This complex compound in allspice seems to do that,” Lokeshwar said. “The most interesting data shows that it actually kills tumor cells which express the very specific prostate cancer marker, the androgen receptor. That is not to say that people should start eating allspice with every meal, but there exists the potential that the slow and steady consumption of this chemo-dietary agent may slow or even prevent prostate cancer.”
For now, Lokeshwar and his study team, including first author Shamaladevi Nagarajarao, Ph.D., a post-doctoral research associate, and Lei Zhang, a graduate student, have demonstrated that Ericifolin kills prostate cancer cells and reduces tumor growth by more than 50 percent in animal models, specifically mice that were injected with prostate cancer cells, then, either fed or injected daily doses of an aqueous allspice extract.
“To our surprise, it worked very well,” Lokeshwar said. “It was surprising because lots and lots of products kill cells in the test tube, but they are not effective when consumed or injected in animal models. In this case, the tumors did not disappear, but they grew about 50 percent more slowly with both methods. Further, these mice did not exhibit any obvious toxicity associated with other anticancer drugs.”
Next the researchers hope to determine whether Ericifolin, a member of the family of polyphenols, the richest source of antioxidants in our diet, can actually prevent prostate cancer from developing altogether. With a $1.5 million NIH grant, they are currently exploring Ericifolin’s anticancer activities — and its translational potential as a cancer chemopreventive agent for humans — in mice that have been genetically programmed to naturally develop prostate cancer at a certain age.
They also hope to begin a clinical trial in the near future with UHealth patients who are under active surveillance for early-stage or slow-growing prostate cancer, which does not yet warrant treatment. Since allspice is not toxic, Lokeshwar reasons those patients would be ideal candidates to take Ericifolin as a daily dietary supplement.
A biologist who began exploring the feasibility of natural anticancer agents about seven years ago, Lokeshwar turned his sights on allspice at the suggestion of a former research associate, Dominic A. Lyn. A co-author on the study, Lyn happened to be from Jamaica, the world’s No. 1 exporter of allspice, which is the dried, unripe berry of Pimenta dioica, an evergreen tree native to Jamaica. “He said, ‘Let’s try allspice. It’s from Jamaica, and it’s unique,’” Lokeshwar recalled.
At the time, there were — and still are — few scientific studies on allspice, but the researchers were intrigued by what they learned: Not only is allspice a popular folk medicine remedy for a number of maladies, but “pound for pound,” Lokeshwar said, “it has the highest amount of antioxidants of any food we know.”
Their interest would escalate when they performed some rudimentary experiments with a jar of allspice powder Lyn borrowed from his wife’s kitchen. Turning the powder into a water extract, they applied it to cancer cells and found it inhibited their growth. More elaborate and sophisticated experiments with allspice purified and liquefied in the Lokeshwar lab would produce the same results, first in cells, then in mice.
The next step, which would prove harder, was pinpointing which of the hundreds of compounds in allspice blocked the antigen receptor. Fortunately, Nagarajarao mistakenly knocked on Lokeshwar’s door inquiring about a job in a different lab. When Lokeshwar learned she was a chemist and biophysicist, he enlisted her in the hunt. With analysis provided by collaborators in the University of Kentucky’s College of Pharmacy, the team eventually isolated Ericifolin as the anticancer agent.
In an intriguing footnote, Zhang, a student in the Sheila and David Fuente Graduate Program in Cancer Biology, has since demonstrated that their aqueous allspice extract also impedes the growth of breast cancer cells, but with a different polyphenol, not Ericifolin. They are not sure yet which one but, in Lokeshwar’s mind, that discovery raises the possibility that allspice may have many anticancer properties worth exploring.
In addition to Lokeshwar, Nagarajarao, Lyn and Zhang, other co-authors of the study, “Ericifolin: a novel antitumor compound from allspice that silences androgen receptor in prostate cancer,” are Khaled A. Shaaban, Ph.D., and Jurgen Rohr, Ph.D., of the University of Kentucky, and Susana Villate, a former research associate in the Department of Urology.
University of Miami