Mechanism for Link Between High Fat Diet and Risk of Prostate Cancer and Disorders Unveiled

ScienceDaily (July 16, 2010) — Prostate cancer is the second leading cause of cancer-related deaths in men with an estimated 192,280 new cases diagnosed in the US in 2009. Diet is considered one of the most important controllable risk factors for inflammation and prostate diseases including benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer.

Sanjay Gupta, MS, PhD, Carter Kissell associate professor & research director in the Department of Urology and associate professor in the Department of Nutrition in the Case Western Reserve School of Medicine, and his team of post-doctoral fellows have focused on understanding the mechanisms of the deleterious effects of a high fat diet on the prostate. Previously, Dr. Gupta's team demonstrated that nuclear factor kappa B (NF-κB), a protein complex that controls DNA transcription which is activated as a result of inflammation and stress, is constitutively activate in human prostate adenocarcinoma and is related to tumor progression (Shukla S et al, Neoplasia, 2004).
In a new study published in the journal The Prostate, Dr. Gupta and his team demonstrate that a high fat diet results in activation of NF-κB in the abdominal cavity, thymus, spleen, and prostate. Non-obese NF-κB reporter mice were fed a high fat diet for four, eight, and 12 weeks. Compared with mice fed a regular diet, the high fat diet group had significant increases in prostate weight, and in the prostate expression of markers of oxidative stress (such as NADPH), and inflammation (such as the downstream targets of NF-κB: nitric oxide synthase, and cyclooxygenase [COX-2]) were increased. These studies provide direct evidence that a high fat diet causes proliferation, inflammation, and oxidative stress that can lead to benign prostatic hyperplasia, prostatitis, and cancer of the prostate, some of the most common disorders affecting adult men.
"Our studies provide evidence that a high-fat diet increases the activation of NF-κB along with elevated levels of NADPH oxidase components which might lead to intraprostatic inflammation. This study strengthens the link between a high-fat diet -- typical of "Western style" high fat diet -- as a potential cause of prostatic diseases including BPG and prostate cancer," said Dr. Gupta.
This work was supported by grants from the National Cancer Institute, the National Center for Complementary and Alternative Medicine, and the Sullivan Foundation for the Study of Prostatitis.

Alex's note:  There are plenty of natural products to control NF-κB 

CHANGING LIFESTYLE CHANGES GENE EXPRESSION A Talk with Dean Ornish

[DEAN ORNISH:] For the last 30 years or so, I have directed a series of clinical research studies proving that the simple choices that we make in our lives each day can have a powerful impact on our health and our well being, and much more quickly than had once been thought possible, even at a cellular level. Ironically, we have been using very high tech, expensive, state of the art measures to prove how powerful very simple and low tech and often ancient interventions can be.


Our prostate study was a randomized control trial of men who had biopsy proven prostate cancer and who have elected not to be treated conventionally for reasons unrelated to our study. What made this interesting from a scientific standpoint is that we could take men who knew they had cancer from biopsies, randomly divide them into two groups, and have a true non-intervention control group so we could determine the effects of comprehensive lifestyle changes alone without being confounded by other treatments. You can't do that with breast cancer because almost everybody gets treated right away, so you don't know if any improvements were due to the lifestyle changes or the chemo or the radiation or the surgery.
After a year we found that PSA levels, a marker for prostate cancer, went up (worsened) in the comparison or control group, but went down significantly (improved) in the experimental group that made the lifestyle changes we recommended. The degree of change in lifestyle was directly correlated with the degree of change in their PSA levels.
We also found that the prostate tumor growth in vitro was inhibited 70 percent in the group that made these changes compared to only nine percent in the group that didn't. The inhibition of the tumor growth was itself a direct function of the degree of change in lifestyle. In other words, the more people changed, the more it directly inhibited the growth of their prostate tumors.
J. Craig Venter has shown that one way you can change your genes is by making new ones. We are finding that another way you can change your gene expression is simply by changing your lifestyle.
In May of this year, we published an article in the Proceedings of the National Academy of Sciences (Craig was the communicating editor). We found that changing lifestyle actually changes gene expression. In only three months, we found that over 500 genes were either up-regulated or down-regulated—in simple terms, turning on genes that prevent many chronic diseases, and turning off genes that cause coronary heart disease, oncogenes that are linked to breast and prostate cancer, genes that promote inflammation and oxidative stress and so on. 

Vitamin E and Prostate Cancer

Vitamin E and Prostate Cancer: A Proteomics Approach Using 2-D Gel Analysis Software

Proteomics can be a useful tool in understanding the anti-cancer activity of vitamin E.

By Christian M. Muenyi, Dr. William L. Stone, Dr. Hamid Kasmai, and Hongsong Yang

Various forms of vitamin E have been under intensive study as chemopreventive and chemotherapeutic agents for a number of cancers.1 Many in vitro, animal, and epidemiological studies have presented evidence of an anti-cancer activity for vitamin E, but there are few studies of vitamin E in prostate cancer,2 and the mechanisms by which forms of vitamin E induce apoptosis in cancer cells remains largely unknown.3 Therefore, proteomics may help to understand the molecular events associated with the cytotoxic effects of vitamin E on cancer cells.


Figure 1: Analysis of 2-D gel by Dymension software showing proteins that are up or down-regulated three hours after delta-tocotrienol treatment.

The purpose of the study was to characterize the proteomic changes occurring in a prostate cancer (LNCaP) cell line after treatment with delta-tocotrienol, a form of vitamin E. In this study, 2-D gel electrophoresis was used to detect changes in protein expression levels associated with this treatment. However, to determine which proteins in a complex 2-D gel image are being expressed requires specialist software to resolve protein spots accurately. Previously, using some 2-D analysis software packages, it was difficult and time consuming to manipulate gel images to obtain meaningful data. To overcome the analysis bottleneck, this article describes how Dymension (Syngene, Frederick, Md.), a 2-D gel image analysis software, can be used to rapidly show which proteins are up or down-regulated by treatment with delta-tocotrienol.