Steroid hormones, which are necessary for male secondary sexual characteristics such as facial and body hair, deepening of the voice, and musculature, are known as androgens. The prostate gland, which is part of the male reproductive system, requires androgens for normal function. With age, the prostate gland is a common source of cancer. In fact, prostate cancer is the most commonly diagnosed form of cancer in men in the United States. Androgens are known to be part of the problem with prostate cancer. If we could prevent prostate cancer from occurring, the devastation this disease causes would be greatly reduced.

Oxygen is necessary for much of life on earth. However, when living cells are given too much oxygen, a condition can be produced that is known as oxidative stress. This is not caused by the oxygen itself, but by forms of the oxygen that are called reactive oxygen species. Oxidative stress in cells can also be produced by exposure to radiation and chemicals. There is evidence that oxidative stress can be involved in the production of some cancers. In our laboratory, we grow prostate cells that came from prostate cancer. When we give these cells low levels of androgens they grow faster, but when we give them levels of androgens normally present in men, they grow slower and oxidative stress is produced. We think this means that men may also have oxidative stress produced in their prostate glands from androgens normally present in their bodies and that this may contribute to prostate cancer. However, we are just beginning to understand how androgens cause the oxidative stress in the prostate cells and how that might lead to cancer.

In our previous studies, we asked how androgens produced oxidative stress in prostate cells. We know that it is not androgens themselves that cause oxidative stress, but changes that occur in cells as a result of being given androgens. Oxygen can be changed to reactive oxygen species by many processes that occur in cells. We found that the part of a cell called the mitochondria was the source of reactive oxygen species that were produced in the prostate cells after androgen exposure. Cells protect themselves by sending signals inside the cell to inform the rest of the cell that reactive oxygen species are present. The way these signals are sent is just starting to be understood, and there are many different kinds of signals that can be sent inside the cell. Part of our research is trying to determine which signals are sent in the prostate cell to inform it that reactive oxygen species are present. So far, we have found two signals that seem to be important called AP-1 and NF-kappaB. Importantly, we found that vitamin E, which can decrease the reactive oxygen species in cells, changed the AP-1 and NF-kappaB signals that were produced by androgen in prostate cells. Several large studies have reported that diets that include compounds that reduce reactive oxygen species can decrease prostate cancer. In one study it was found that men taking vitamin E were less likely to develop prostate cancer. It is possible that vitamin E may prevent the occurrence of prostate cancer by altering the changes that are produced by reactive oxygen species in the prostate gland as a result of androgen exposure.

We would like to continue to study the changes that occur in prostate cells due to oxidative stress resulting from exposure to androgens and what effects vitamin E has on these changes. First, we will look at the role of AP-1 and NF-kappaB signals in the response of prostate cells to androgens. Since cells have defense mechanisms that are changed by reactive oxygen species, we will study changes in these defense mechanisms in these cells. We will also look at whether damage that occurs from reactive oxygen species can be found in these cells. Then we will add vitamin E in these studies to see if it can alter changes in the defense mechanisms and damage. Finally, since the work we have previously done was with prostate cancer cells that have many changes compared to normal cells, we will determine whether or not androgen exposure can produce oxidative stress in normal human prostate cells and what effect vitamin E may have on oxidative stress in these cells. These studies will be important for helping us understand how oxidative stress may be involved in prostate cancer and may help us find better ways of preventing prostate cancer development.