POMEGRANATE JUICE & PROSTATE CANCER
to the American Cancer Society, an estimated 186,000 men will
be diagnosed with prostate cancer in the
Biologically active compounds in pomegranate juice, known as ellagitannins, are known to have powerful antioxidant and anti-inflammatory effects. These powerful dietary antioxidants are related, chemically, to the antioxidants also found in green tea, which is another area of intense focus in cancer prevention research (please review my archived columns for reviews of important and recently published research on the potential health effects of green tea).
Previous research studies, looking at human prostate cancer cells growing in cell cultures, and implanted in mice as well, have suggested potential cancer prevention and cancer treatment roles for pomegranate juice extracts. In a recently published clinical study, pomegranate juice supplements were found to slow down the progression of recurrent prostate cancer in patients who had previously undergone treatment with surgery or radiation therapy. Moreover, when the serum of these patients was added to cell cultures containing human prostate cancer cells, the serum collected after patients consumed pomegranate juice both slowed down the growth of the prostate cancer cells and increased the death rate of these same cells.
A new research study, just published in the journal Molecular Cancer Therapeutics by scientists at UCLA, adds important new information about the possible role of pomegranate juice in the prevention and treatment of prostate cancer.
Nuclear Factor Kappa-B, or NF-κB, consists of a group of proteins referred to, collectively, as transcription factors. Transcription factors act by activating multiple genes in both normal cells and cancer. Activation of the NF-κB signaling pathway turns on a variety of genes that appear to play an important role in the development and progression of many cancers, including prostate cancer. NF-κB has also been implicated in the effects of chronic inflammation on the development of several cancers, including prostate cancer. Moreover, activation of NF-κB also appears to enable cancer cells to resist the effects of chemotherapy and other cancer treatments, and appears to be linked with more aggressive tumor biology, and a resulting increase in the risk of cancer recurrence.
While almost all prostate cancer cells are initially sensitive to hormonal therapies that block the male sex hormones (androgens), patients with advanced prostate cancer who are treated with androgen blocking agents will eventually develop prostate cancer cells that are resistant (or androgen-independent) to such therapies. When metastatic prostate cancer tumors become androgen-independent, these tumors then become unresponsive to most clinical therapies.
In this study, pomegranate extract was added to androgen-independent human prostate cancer cells in the laboratory, resulting in an inhibition of NF-κB that was proportional to the amount of pomegranate extract that was added. This inhibition of the NF-κB pathway, which was induced by pomegranate extract, also resulted in a decreased rate of growth of the androgen-independent prostate cancer cells, as well as an increased death rate among these cells.
When androgen-sensitive human prostate cancer tumors are transplanted into mice, they gradually become androgen-independent following castration of the mice. In this research study, the authors also implanted androgen-sensitive human prostate cancer cells into laboratory mice. Some mice were given pomegranate extract or pomegranate juice, while other mice were not given any pomegranate supplements. Subsequently, as the transplanted prostate cancer cells began to grow into tumors, all mice were then castrated to induce androgen insensitivity in their implanted tumors. The authors subsequently found that the mice that had received pomegranate supplements developed significantly smaller tumors when compared to the mice that had not received pomegranate extract. Moreover, the development of androgen insensitive tumors was significantly delayed in the mice that had received the pomegranate supplement, suggesting that pomegranate extract may not only be able to shrink prostate cancer tumors, but may also be able to maintain prostate cancer cells in the more favorable androgen-sensitive state. PSA levels in the blood of the mice that received the pomegranate extract were also significantly lower than what was observed in the control animals that did not receive the extract in their diets. All of these favorable effects that were observed in the mice that had received pomegranate extract appeared to be linked directly to an inhibition of the NF-κB signaling pathway.
The results of this study are highly intriguing, as they suggest that, at least in mice, pomegranate extracts may be able to slow prostate cancer cell growth, as well as significantly delaying the transition of prostate tumors from the more favorable androgen-sensitive state to the treatment-resistant androgen-insensitive state. Because rising levels of NF-κB activity have previously been linked to the development of prostate cancer, as well as to the increased biological aggressiveness of prostate cancer cells, the inhibition of NF-κB with pomegranate extracts could conceivably reduce the risk of developing prostate cancer and might also reduce the growth rate and aggressiveness of already established prostate cancer. Additionally, and importantly, the results of this study suggest that NF-κB, itself, probably plays a dominant role in the development of androgen independence in prostate cancer tumors, and, therefore, that blocking NF-κB with pomegranate extract may maintain metastatic prostate cancer tumors in the more treatable androgen-sensitive state.
But, before you go to your local grocery store and buy all of the pomegranates that they have in stock, there are a couple of important caveats that must be mentioned. First, as I always note with laboratory studies that involve cells growing in a Petrie dish, or tumor cells implanted into laboratory animals, there is absolutely no guarantee that human patients will respond in the same ways as were observed in the laboratory. A second caveat is that the mice utilized in this research study were fed the daily equivalent of 10 times as much pomegranate extract and juice as an ordinary human is likely to take in a day. Whether or not smaller and more reasonable amounts of pomegranate supplementation will produce the same beneficial effects (in either mice or humans!) remains to be seen.
this study was supported with funding from the dominant producer
of pomegranates and pomegranate juice in the
Although the results of this study cannot tell us if pomegranate juice is able to either prevent prostate cancer in humans or decrease its aggressiveness once it has already developed, there have been very few reports of any apparent serious ill affects associated with pomegranate juice consumption. And so, for most people, a swig or two of pomegranate juice a day shouldn’t be a problem. However, you should still check with your physician before consuming significant quantities of pomegranate juice, as there have been some reports of adverse reactions involving heart and cholesterol-lowering medications (pomegranate juice appears to increase the blood levels of certain medications, which may lead to significant adverse health reactions).
Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
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Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
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