RxPG News : Omega 3 Fatty Acids

Omega-3 fatty acids inhibit growth of liver cancer cells

Mon, 03 Apr 2006 14:57:37 PST

( from http://www.rxpgnews.com ) Two new studies by a University of Pittsburgh research team suggest that omega-3 fatty acids--substances that are found in high concentrations in fish oils and certain seeds and nuts--significantly inhibit the growth of liver cancer cells. The studies, presented today at the annual meeting of the American Association for Cancer Research (AACR), at the Washington Convention Center in Washington, D.C., suggest that omega-3 fatty acids may be an effective therapy for both the treatment and prevention of human liver cancers.

The first study, Abstract number 2679, looked at the effect and mechanism of omega-3 and omega-6 polyunsaturated fatty acids in human hepatocellular carcinoma cells. Hepatocellular carcinoma accounts for 80 to 90 percent of all liver cancers and is usually fatal within three to six months of diagnosis.

"It has been known for some time that omega-3 fatty acids can inhibit certain cancer cells. So, we were interested in determining whether these substances could inhibit liver cancer cells. If so, we also wanted to know by what mechanism this inhibition occurs," said Tong Wu, M.D., Ph.D., a member of the division of transplantation pathology, University of Pittsburgh School of Medicine, in whose laboratory the research was conducted.

The investigators treated the hepatocellular carcinoma cells with either the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or the omega-6 fatty acid arachidonic acid (AA), for 12 to 48 hours. DHA and EPA treatment resulted in a dose-dependent inhibition of cell growth, whereas AA treatment exhibited no significant effect.

According to the investigators, the effect of omega-3 fatty acids on cancer cells likely is due to the induction of apoptosis, or programmed cell death. Indeed, the investigators found that DHA treatment induced the splitting up, or cleavage, of an enzyme in the cell nucleus known as poly (ADP-Ribose) polymerase, or PARP, which is involved in repairing DNA damage, mediating apoptosis and regulating immune response. The cleavage of this enzyme is considered a tell-tale indicator of apoptosis. Furthermore, DHA and EPA treatment indirectly decreased the levels of another protein known as beta-catenin, an overabundance of which has been linked to the development of various tumors.

"Beta-catenin is known to promote cell growth and also is implicated in tumor cell promotion. Therefore, our finding that omega-3 fatty acids can decrease levels of beta-catenin is further evidence that these compounds have the ability to interact on several points of pathways involved in tumor progression," explained Dr. Wu.

In the second study, Abstract number 2680, the investigators treated cholangiocarcinoma tumor cells with omega-3 and omega-6 fatty acids for 12 to 48 hours. Cholangiocarcinoma is a particularly aggressive form of liver cancer that arises in the ducts that carry bile from the liver and has an extremely high mortality rate. Again, the omega-3 fatty acids DHA and EPA treatments resulted in a dose-dependent inhibition of cancer cell growth, while the omega-6 fatty acid AA treatment had no significant effect. Likewise, DHA treatment induced a cleavage form of PARP in cholangiocarcinoma cells, and DHA and EPA treatment significantly decreased the level of beta-catenin protein in the cells.

According to Dr. Wu, these findings suggest that omega-3 fatty acids not only may be an effective therapy for the treatment of human liver cancers but may also be a means of protecting the liver from steatohepatitis, a chronic liver disease characterized by the buildup of fat in the liver and believed to be a precursor of hepatocellular carcinoma. The next step in the process, he said, is to test the effects of omega-3 fatty acids in mice harboring human liver tumors.

Researchers create pigs that produce heart-healthy omega-3 fatty acids

Mon, 27 Mar 2006 00:53:37 PST

( from http://www.rxpgnews.com ) Researchers report they have created pigs that produce omega-3 fatty acids, which are known to improve heart function and help reduce the risks for heart disease, representing the first cloned transgenic livestock in the world that can make the beneficial compound. The research could be a boost to both farmers and health-conscious consumers seeking an alternative and safer source of omega-3 fatty acids. Currently, the only way for humans to realize the benefits of omega-3 fatty acids is by taking dietary supplements or by eating certain types of fish that may also contain high levels of mercury.

The results, which are being published by Nature Biotechnology, are the work of a team assembled by Yifan Dai, M.D., Ph.D., of the University of Pittsburgh School of Medicine that includes researchers from Randy Prather, Ph.D.'s group at the University of Missouri-Columbia (MU) National Swine Resource and Research Center, the laboratory of Jing X. Kang, M.D., Ph.D., at Massachusetts General Hospital (MGH), and the laboratories of Dr. Dai and Rhobert Evans, Ph.D., at the University of Pittsburgh.

To stimulate production of omega-3 fatty acids in pigs, a team led by Dr. Dai transferred a gene known as fat-1 to pig primary fetal fibroblasts, the cells that give rise to connective tissue. Dr. Prather's group then created the transgenic pigs from these cells using a method called nuclear transfer cloning. The transgenic pig tissues were then analyzed for omega-3 fatty acids in Dr. Kang's lab at MGH and by Drs. Dai and Evans at Pitt. The fat-1 gene is responsible for creating an enzyme that converts less desirable, but more abundant, omega-6 fatty acids in the animals to omega-3 fatty acids. The results could lead to a better understanding of cardiovascular function not only in pigs, but in humans as well.

"Pigs and humans have a similar physiology," said Dr. Prather, distinguished professor of reproductive biology in MU's College of Agriculture, Food and Natural Resources and a corresponding author with Dr. Dai. "We could use these animals as a model to see what happens to heart health if we increase the omega-3 levels in the body. It could allow us to see how that helps cardiovascular function. If these animals are put into the food chain, there could be other potential benefits. First, the pigs could have better cardiovascular function and therefore live longer, which would limit livestock loss for farmers. Second, they could be healthier animals for human consumption."

"While fish, especially salmon and tuna, is one of the best food sources of omega-3 fatty acids, we have been warned to limit consumption because of high mercury levels. These animals could represent an alternative source as well as be an ideal model for studying cardiovascular disease and autoimmune disorders," said Dr. Dai, an associate professor of surgery at the University of Pittsburgh School of Medicine's Thomas E. Starzl Transplantation Institute.

"Livestock with a health ratio of omega-3 to omega-6 fatty acids may be a promising way to re-balance the modern diet without relying solely on diminishing fish supplies or supplements," Dr. Kang said.

The transgenic pigs were created using technology developed by Dr. Kang of MGH, an associate professor of medicine at Harvard Medical School and co-lead author of the current report with MU's Liangxue Lai, Ph.D. Dr. Kang's group created the first omega-3 rich mammals (mice) and published that work in Nature in 2004. Because of this earlier study, Dr. Dai initiated the collaboration with the aim of creating cloned transgenic pigs capable of making omega-3 fatty acids.

The production of these pigs will now provide researchers with opportunities to conduct studies not previously possible. For example, researchers in MU's College of Veterinary Medicine department of biomedical sciences now plan to study the omega-3 pigs. Harold Laughlin, Ph.D., department chair, uses pigs to study the cardiovascular benefits of exercise because a pig's cardiovascular system is similar to a human's. Now he plans to incorporate these unique pigs into his research to determine how higher omega-3 levels and exercise could affect the cardiovascular system.

Evidence for omega 3 fats less conclusive: Systematic Review

Fri, 24 Mar 2006 13:25:37 PST

( from http://www.rxpgnews.com ) A study published online by the BMJ today doesn't find evidence of a clear benefit of omega 3 fats on health.

These findings do not rule out an important effect of omega 3 fats, but suggest that the evidence should be reviewed regularly, say the researchers.

Consumption of long chain omega 3 fatty acids, found in oily fish and fish oils, and a shorter chain omega 3, found in some plant oils, is thought to protect against heart disease. UK guidelines encourage the general public to eat more oily fish, and higher amounts are advised after a heart attack.

Researchers analysed 89 studies (48 randomised controlled trials and 41 cohort studies) to assess the health effects of long and short chain omega 3 fats on total mortality, cardiovascular events, cancer, and strokes.

Each study involved a treatment group and a control group and investigated the effect of omega 3 intake on health for at least six months. Differences in study quality were taken into account to identify and minimise bias.

Pooling the results showed no strong evidence that omega 3 fats have an effect on total mortality or combined cardiovascular events. The few studies at low risk of bias were more consistent, but they also showed no effect of omega 3 on total mortality or cardiovascular events.

When data on long chain omega 3 fats were analysed separately, total mortality and cardiovascular events were not reduced. No study showed increased risk of cancer or stroke with higher intake of omega 3, but there were too few events to rule out important effects.

Other recent reviews of omega 3 trials found that omega 3 fats decrease mortality, but the publication of a large contradictory trial has changed the overall picture. The authors cannot say exactly why the results of this trial differ from the other large studies in this field.

They therefore conclude that it is not clear whether long chain or short chain omega 3 fats (together or separately) reduce or increase total mortality, cardiovascular events, cancer, or strokes.

UK guidelines advising people to eat more oily fish should continue at present but the evidence should be reviewed regularly, say the authors. However, it is probably not appropriate to recommend a high intake of omega 3 fats for people who have angina but have not had a heart attack.

To understand the effects of omega 3 fats on health, we need more high quality randomised controlled trials of long duration that also report the associated harms, they conclude.

We are faced with a paradox, says Eric Brunner in an accompanying editorial. Health recommendations advise increased consumption of oily fish and fish oils. However, industrial fishing has depleted the world's fish stocks by some 90% since 1950, and rising fish prices reduce affordability particularly for people with low incomes.

Global production trends suggest that, although fish farming is expanding rapidly, we probably do not have a sustainable supply of long chain omega 3 fats, he warns.

Omega-3 Fatty Acids in Oily Fish like Salmon could block Prostate Cancer

Thu, 23 Mar 2006 18:00:37 PST

( from http://www.rxpgnews.com ) Omega-3 oil present in fish like salmon could block prostate cancer, scientists have found.

Prostate cancer is a disease in which cancer develops in the prostate, a gland in the male reproductive system. It may also spread from the prostate to other parts of the body, especially the bones and lymph nodes.

People in this disease suffer pain, difficulty in urinating and erectile dysfunction.

The disease only occurs in men and develops most frequently in individuals over 50 years old. It is the second most common type of cancer in men and it is responsible for more deaths than any other cancer except lung cancer.

Previous research suggested that omega-3 fats, which are also found in mackerel and fresh tuna, may help cut the risk of cancer and heart disease.

The Paterson Institute researchers at Manchester's Christie Hospital have now found that eating a diet with the right balance of omega-3 and omega-6 fats may well help to keep prostate cancer within the prostate gland.

Omega-6 fats, found in vegetable oils, nuts and seeds, play a key role in keeping us healthy. However, while omega-6 fats increased the spread of prostate cancer cells into bone marrow, omega-3 fats blocked this, the researchers said.

"It is possible to have a healthy balance of these two types of fat - we only need about half as much omega-3 as omega-6 - that will still stop cancer cells from spreading," researcher Mick Brown said.

Omega 3 fatty acids influence mood, impulsivity and personality

Sat, 04 Mar 2006 15:59:37 PST

( from http://www.rxpgnews.com ) Omega-3 polyunsaturated fatty acids may influence mood, personality and behavior, according to results of a study presented today by University of Pittsburgh School of Medicine researchers at the 64th Annual Scientific Meeting of the American Psychosomatic Society in Denver.

In a study of 106 healthy volunteers, researchers found that participants who had lower blood levels of omega-3 polyunsaturated fatty acids were more likely to report mild or moderate symptoms of depression, a more negative outlook and be more impulsive. Conversely, those with higher blood levels of omega-3s were found to be more agreeable.

"A number of previous studies have linked low levels of omega-3 to clinically significant conditions such as major depressive disorder, bipolar disorder, schizophrenia, substance abuse and attention deficit disorder," said Sarah Conklin, Ph.D., a postdoctoral scholar with the Cardiovascular Behavioral Medicine Program in the department of psychiatry at the University of Pittsburgh School of Medicine. "However, few studies have shown that these relationships also occur in healthy adults. This study opens the door for future research looking at what effect increasing omega-3 intake, whether by eating omega-3 rich foods like salmon, or taking fish-oil supplements, has on people's mood."

The American Heart Association recommends that all Americans consume fish, which is high in omega-3 fatty acids, twice per week. This recommendation is based upon evidence that a diet high in fish s associated with improved heart health and reduced risk for heart-related problems. While the cardiovascular benefit of increasing omega-3 intake is well recognized, relatively little is known of the potential mental health effects among the general public.

Comparisons were made by analyzing levels of omega-3 fatty acids in participants' blood and comparing that data to the participants' scores on three accepted tests for depression, impulsiveness and personality. The amount of omega-3 circulating in blood reflects dietary intake of the fatty acid. The study did not require participants to make changes in their normal diet habits.

Omega-3 and Propofol Combination offers hope for new anti-breast cancer drugs

Wed, 08 Jun 2005 19:42:38 PST

( from http://www.rxpgnews.com ) Omega-3, the fatty acid found in oily fish, could be combined with a commonly used anesthetic to develop drugs to treat breast cancer, according to research published today in the journal Breast Cancer Research.

Compounds of Omega-3 fatty acids and propofol reduce the ability of breast cancer cells to develop into malignant tumours, inhibiting cancer cell migration by 50% and significantly reducing their metastatic activity. These new compounds could be developed into a new family of anti-cancer drugs.
Dr Rafat Siddiqui, from the Methodist Research Institute and Indiana University in Indianapolis, and his colleagues studied the effect of two Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), combined with propofol on a breast cancer cell line in vitro. Omega-3 fatty acids such as DHA and EPA have a minimal effect on cancer cells when applied alone. Propofol is a potent anti-oxidant known to inhibit cancer cell migration by only 5-10%.

The results of the study show that propofol and DHA or EPA have a much more significant effect on cancer cells when used in combination, as conjugates, than when used alone. The conjugates inhibit cancer cell adhesion by 15% and 30% respectively, reduce cell migration by 50% and increase apoptosis by 40%.

"These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer" conclude Siddiqui and colleagues.

Malignant cancer cells are highly invasive cells that have lost the ability to sense cues from their environment. As a result, they start dividing abnormally, migrate and accumulate into malignant tumours, in a process called metastasis, which is potentially life-threatening. The aim of anti-cancer drugs is therefore to prevent the cells from dividing abnormally and from spreading, to kill the cells, or to cause the cells to kill themselves.

Fatty acids are often attached to drugs, because they facilitate the absorption of the drugs by the cells. Siddiqui and colleagues explain that DHA and EPA might have had this effect on propofol. They add "It is possible that these conjugates provide a mechanism whereby propofol can be retained in cell membranes for a longer duration and therefore enhance its anticancer effects".

Omega-3 fatty acids, like those found in oily fish such as tuna, salmon, herring, sardines and mackerel, are already known to have many positive health benefits. They are commonly recommended for maintaining a healthy heart, as they are known to reduce cholesterol levels and thought to help prevent cardiovascular disease. Research suggests that Omega-3 may also protect against arthritis, lupus, and asthma and help people with biopolar disorder.