We have recently published further studies of the effects of BPA, including the observation that curcumin, the active ingredient in the spice turmeric, can reduce the effects of BPA (bisphenol-A). Both the abstract [click here] and the full article [click here] are on line and can be downloaded free.
This article underscores the connection between BPA and increased cell growth that we suspected from our first studies over five years ago and suggests that curcumin, or a similar drug, may be useful to reverse the effects of BPA.
Looking at cells before they are cancerous.
There is a lot of research looking at how BPA affects cancer cells, but that doesn’t help us understand the origins of cancer because the cells are already cancer. To study the origins of cancer you have to start with benign cells.
In our research, we start with cells that are not cancerous and look at what BPA does to these cells. We have identified two ways that BPA changes non-cancerous cells and makes them behave like cancer cells.
BPA stimulates cell growth.
Non-cancerous breast cells usually grow slowly. Estrogens stimulate these cells to grow faster, and this is part of the way that estrogens and the synthetic estrogen, DES, contribute to breast cancer.
BPA stimulates growth of non-cancerous breast cells just like estrogens.
The worry is that, once stimulated by BPA, some cells will continue to grow on their own.
Encountering our worst fear.
In this paper we report the event that we all fear: some non-cancerous cells continued to grow unusually well even after the BPA was gone. This is the kind of uncontrolled cell growth that could lead to cancer.
Fortunately, this was a rare event, but remember that not everyone exposed to any cancer-causing agent gets cancer. For example, radiation exposure is a risk factor for many cancers, but only a small fraction of the people who are exposed to radiation go on to get cancer. In fact, it would be suspicious if all of our cells continued to grow after BPA was removed. However, that it happened even one time reinforces the parallel to other dangerous exposures.
BPA helps cells stay alive.
When the body is functioning normally, damaged cells go away by a process called apoptisis (ay-pah-TOE-sis) or programmed cell death. Although it is called “cell death” apoptosis is really a special way that damaged or unnecessary cells break up and go away. All cells are capable of this. It is a little like a scuttle on a ship.
Apoptosis is important because it is the way that cells damaged by radiation, chemotherapy, or hormone therapy go away. If apoptosis does not work, cells can continue to grow abnormally and not die. This happens in cancer, and in fact, evasion of apoptosis is a prerequisite for a cell to become malignant.
BPA causes cells to evade apoptosis.
When we exposed cells to tamoxifen, they should have undergone apoptosis, but they did not. This means that BPA gives cells the ability to grow when they should be stopped by anti-cancer or cancer preventing drugs. This brings these non-cancerous cells potentially closer to being malignant, especially if the effects persist after the BPA is gone, as we found for growth of some cells.
The Curcumin Connection
Curcumin is the chemical in the spice, turmeric, that makes curry yellow. It is a traditional remedy in many cultures, and it has thousands of years of use to suggest that it is safe.
For the last 20 years, researchers have wondered if curcumin might have direct anti-cancer effects. Relevant to our research, these researchers found that curcumin directly affects the same genes that are controlled by mTOR, but it has the opposite effects from BPA. Curcumin makes cells less likely to grow and more likely to undergo apoptosis.
This research suggested that, even if BPA activated mTOR, curcumin might reverse the effects because it directly blocks the same genes that mTOR activates – in essence, it looked like curcumin might “do an end run” and reverse the effects of BPA.
We found just that. Curcumin reversed the effects of BPA that made cells grow abnormally and survive if they were damaged. Most important, the cells that kept growing after the BPA was removed, were also stopped by curcumin.
There are two important conclusions from this study.
Convince the skeptics.
Scientists influence official beliefs about environmental chemicals. However, scientists tend to be skeptical. They want to know, “How does BPA work?” We can now answer their question. We can show that BPA modifies activity of known genes, and then we add that a known blocker of those genes, i.e. curcumin, reverses the effects of BPA. This is the kind of add-then-subtract double proof that scientists demand.
The situation is not hopeless.
It may not be possible to eat enough curry to reverse the effects of BPA, but it is important to know that the effects are not irreversible. [Supplements of curcumin are on the market, but there is no data yet on how much curcumin you would need to take to protect yourself from BPA.]
Demonstrating reversal of the effects of BPA provides a tangible goal as we try to prevent breast cancer and other effects of endocrine disruption in humans. We need to know it is possible to help.
Should we eat more curry?
Yes, eat more curry if you like it. Know that it might help, but we don’t know yet how much it might take to be beneficial. Researchers are working on that.
A complete pathway.
This study completes a picture of how abnormal activation of a series of genes in a whole pathway can cause cells to grow abnormally. For more discussion of cell pathways, see Perspectives on Womens’ Health from August 21, 2012. [click here]
For those who want to read more, the effects of BPA on major genes include:
Increased PI3K, AKT, mTOR, and cyclins and decreased PTEN and p53.