Study: Do antioxidants encourage the spread of cancer cells?

IN DEPTH REVIEW OF RESEARCH

Study background: 

Cells undergo a process called metastasis to spread from a primary tumor to other sites in the body. Few cancer cells can survive the metastasis process to spread and grow at another site in the body. It is not fully understood how cells that manage to metastasize are able to do so. Dr. Sean Morrison and colleagues at the University of Texas Southwestern Medical Center looked at the capability of metastasized melanoma cells to withstand oxidative stress. (Oxidative stress, which can damage cells, occurs when an imbalance develops between reactive oxygen species (ROS) and the body’s ability to remove them.) ROS occurs naturally in the body as oxygen is processed; they are damaging, but our bodies usually have a sufficiently strong system response to handle it. ROS increase during times of environmental stress, such as exposure to ultraviolet (UV) light or ionizing radiation. Molecules called antioxidants play a role in controlling ROS.  Antioxidants are produced by the body and are also found in many different foods. Some antioxidants are sold as over-the-counter dietary supplements.

Researchers of this study wanted to know:

How oxidative stress and antioxidants affect the ability of melanoma cells to metastasize.

Population(s) looked at in the study:

Cancer cells from four patients with non-metastatic melanoma and four patients with metastasized melanoma were injected into mice that lacked functioning immune systems.

Study findings: 

1. Changes in melanoma cells in the blood and at distant points from the primary tumor indicated oxidative stress that was not found in the rodent’s primary tumors. 
2. Melanoma cells that successfully metastasized withstood oxidative stress. 
3. Large doses of the antioxidant N-acetyl cysteine (NAC) promoted metastasis.

Limitations:

This study was done in mice that did not have functioning immune systems, allowing researchers to inject and study human tumor cells in a mouse model. Though the researchers used melanoma cells from human patients samples, observing what happens when they were transplanted into immunodeficient mice does not exactly correlate to what happens in human cancer patients with functional immune systems. In addition, the number of different patient samples used in this study was relatively low, which means that there is a possibility that the results the researchers see are unique to those tumors. Researchers did note that melanoma metastasis in the study mice is predictive of clinical outcomes—in other words, the cancer cells that metastasized in human patients also metastasized in the mice. While this may be true, it does not mean that the mechanism that the cells use to metastasize is exactly the same in the two species, or that a functional immune system may affect the process.  

Conclusions:

Not too long ago, the idea that antioxidants are beneficial was well received, and clinical trials looked at giving cancer patients supplementary antioxidants. Recently, however, this idea is being questioned. This study indicates that oxidative stress limits the ability of melanoma cells to metastasize; when researchers added antioxidants to relieve oxidative stress, more metastasis occurred. The antioxidant treatments used in these mouse studies may help us understand how cancer acts, but the path from antioxidant treatments in genetically altered mice to clinical application is a long one, and not all study results in mice hold true in human patients. More work needs to be done to fully understand this process and how it might impact cancer patients.

However, the data from previous clinical trials prompted the U.S. Preventive Services Task Force (USPSTF) to recommend against the use of Vitamin E and Beta-carotene (antioxidants) for the prevention of cardiovascular disease or cancer. The USPSTF also says that there is not enough data to recommend for or against the use of multivitamins (which include antioxidants) for the prevention of cardiovascular disease or cancer.

It is also important to note that the antioxidants injected into mice in this study were pure, supplemental treatment antioxidants. They included much greater antioxidant levels than what a person would get from a normal, healthy diet. In the context of this study, a greater dose of treatment antioxidants promoted metastasis. People with cancer, and those who have a high risk of cancer, should continue to eat a healthy diet that includes a variety of fruits and vegetables.

posted 12/01/15