Health for life

Resveratrol, a compound found commonly in grape skins and red wine, has been shown to have several beneficial effects on human health, including cardiovascular health and stroke prevention. Now, a University of Missouri researcher has discovered that the compound can make prostate tumor cells more susceptible to radiation treatment, increasing the chances of a full recovery from all types of prostate cancer, including aggressive tumors.


"Other studies have noted that resveratrol made tumor cells more susceptible to chemotherapy, and we wanted to see if it had the same effect for radiation therapy," said Michael Nicholl, an assistant professor of surgical oncology in the MU School of Medicine. "We found that when exposed to the compound, the tumor cells were more susceptible to radiation treatment, but that the effect was greater than just treating with both compounds separately."

Prostate tumor cells contain very low levels of two proteins, perforin and granzyme B, which can function together to kill cells. However, both proteins need to be highly "expressed" to kill tumor cells. In his study, when Nicholl introduced resveratrol into the prostate tumor cells, the activity of the two proteins increased greatly. Following radiation treatment, Nicholl found that up to 97 percent of the tumor cells died, which is a much higher percentage than treatment with radiation alone.

"It is critical that both proteins, perforin and granzyme B, are present in order to kill the tumor cells, and we found that the resveratrol helped to increase their activity in prostate tumor cells," Nicholl said. "Following the resveratrol-radiation treatment, we realized that we were able to kill many more tumor cells when compared with treating the tumor with radiation alone. Its important to note that this killed all types of prostate tumor cells, including aggressive tumor cells."

Resveratrol is present in grape skins and red wine and available over-the-counter in many health food sections at grocery stores. However, the dosage needed to have an effect on tumor cells is so great that many people would experience uncomfortable side effects.

"We dont need a large dose at the site of the tumor, but the body processes this compound so efficiently that a person needs to ingest a lot of resveratrol to make sure enough of it ends up at the tumor site. Because of that challenge, we have to look at different delivery methods for this compound to be effective," Nicholl said. "Its very attractive as a therapeutic agent since it is a natural compound and something that most of us have consumed in our lifetimes."

Nicholl said that the next step would be to test the procedure in an animal model before any clinical trials can be initiated. Nicholls studies were published in the Journal of Andrology and Cancer Science. The early-stage results of this research are promising. If additional studies, including animal studies, are successful within the next few years, MU officials will request authority from the federal government to begin human drug development (this is commonly erred to as the "investigative new drug" status). After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for cancer.

Resveratrol is a naturally occurring dietary compound found in grapes, berries, and peanuts. This polyphenol protects plants against pathogens such as bacteria and fungi by inducing cell death in invading organisms. The compound was discovered in red wine in 1939 but by and large did not attract the attention of the scientific community. More recently, pre-clinical studies have revealed the many beneficial properties of resveratrol. These include antidiabetic, cardioprotective, and chemopreventive effects. The latter has been associated to resveratrol antioxidant and anti-inflammatory proprieties.

A number of studies show that resveratrol induces cell death in different types of cancers, both in humans and animal models. However, the potential anti-tumor effect of resveratrol is still little understood as the compound seems to induce cell death in a number of cancer cells whereas in others no effect is observed, even when massive doses of resveratrol are used. A phase I study on the pharmacokinetic properties of resveratrol as a potential cancer chemopreventive agent has concluded that consumption of high levels of resveratrol would be insufficient to provide the amounts of resveratrol needed to elicit its chemopreventive proprieties. Nevertheless, a few ongoing clinical trials investigate the effects of resveratrol on a number of diseases, including colon cancer.

More recently, the anti-tumor functions of resveratrol have been associated to p53, a protein responsible for suppressing tumor development in the body. p53 is one of the main blockers of the cell cycle, leading cells to the death row. A faulty p53 is unable to suppress cell growth, which ultimately results in tumor development. Indeed, studies have shown that p53 is either defective or simply absent in most cancers.

To investigate whether resveratrol anti-tumor effects, as observed in some cancer cell lines, depend on the status of the cells p53 gene, a group led by Dr Jerson L. Silva at the Universidade Federal do Rio de Janeiro, Brazil, tested the effects of resveratrol in H1299, a human non-small lung carcinoma cell line carrying only a partial fragment of the p53 gene and compared the results with MCF-7, A549, and H460, which are cancer cell lines carrying normal copies of p53. The study shows that although resveratrol affects the viability of all cancer cell lines, MCF-7, A549, and H460 are more sensitive to the effects of resveratrol than H1299. While MCF-7 cell lines die after exposure to resveratrol, H1299 remains resistant. Additional findings indicate that the toxic effect of resveratrol on MCF-7, A549, and H460 cell lines is mediated by p53.

The research group then went one step further and asked what would happen if a normal copy of p53 is added to the previously p53-defective H1299 cancer cell line. The results, published this week in PLOS ONE, show that introduction of a normal copy of p53 in H1299 turns the cell line sensitive to the anti-tumor effects of resveratrol, similarly to that observed in other cancer cell lines (MCF-7, A549, and H460). "Our findings may have potential applications in cancer cell lines that are under p53 control," says Dr Danielly Ferraz da Costa, the first author of the study. "Also, the introduction of the p53 gene in p53-defective tumors, followed by resveratrol treatment, may represent a novel and promising therapeutic approach in our fight against cancer," says the young author.

Studies have shown that resveratrol, a natural compound found in colored vegetables, fruits and especially grapes, may minimize the impact of Parkinson’s disease, stroke and Alzheimer’s disease in those who maintain healthy diets or who regularly take resveratrol supplements. Now, researchers at the University of Missouri have found that resveratrol may also block the effects of the highly addictive drug, methamphetamine.

Dennis Miller, associate professor in the Department of Psychological Sciences in the College of Arts & Science and an investigator with the Bond Life Sciences Center, and researchers in the Center for Translational Neuroscience at MU, study therapies for drug addiction and neurodegenerative disorders. Their research targets treatments for methamphetamine abuse and has focused on the role of the neurotransmitter dopamine in drug addiction. Dopamine levels in the brain surge after methamphetamine use; this increase is associated with the motivation to continue using the drug, despite its adverse consequences. However, with repeated methamphetamine use, dopamine neurons may degenerate causing neurological and behavioral impairments, similar to those observed in people with Parkinson’s disease.

“Dopamine is critical to the development of methamphetamine addiction—the transition from using a drug because one likes or enjoys it to using the drug because one craves or compulsively uses it,” Miller said. “Resveratrol has been shown to regulate these dopamine neurons and to be protective in Parkinson’s disease, a disorder where dopamine neurons degenerate; theore, we sought to determine if resveratrol could affect methamphetamine-induced changes in the brain.”

Using procedures established by Parkinson’s and Alzheimer’s disease research, rats received resveratrol once a day for seven days in about the same concentration as a human would receive from a healthy diet. After a week of resveratrol, researchers measured how much dopamine was released by methamphetamine. Researchers found that resveratrol significantly diminished methamphetamine’s ability to increase dopamine levels in the brain. Furthermore, resveratrol diminished methamphetamine’s ability to increase activity in mice, a behavior that models the hyperactivity observed in people that use the stimulant.

“People are encouraged by physicians and dieticians to include resveratrol-containing products in their diet and protection against methamphetamine’s harmful effects may be an added bonus,” Miller said. “Additionally, there are no consistently effective treatments to help people who are dependent on methamphetamine. Our initial research suggests that resveratrol could be included in a treatment regimen for those addicted to methamphetamine and it has potential to decrease the craving and desire for the drug. Resveratrol is found in good, colorful foods, and has few side effects. We all ought to consume resveratrol for good brain health; our research suggests it may also prevent the changes in the brain that occur with the development of drug addiction.”

The study “Repeated resveratrol treatment attenuates methamphetamine-induced hyperactivity and [3H]dopamine overflow in rodents,” was published in Neuroscience Letters.

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