Fish/Fish Oil: Cancer Benefits

Omega-3 fatty acids could aid cancer prevention and treatment

Omega-3 fatty acids, contained in oily fish such as salmon and trout, selectively inhibit growth and induce cell death in early and late-stage oral and skin cancers, according to new research from scientists at Queen Mary, University of London published online in the journal Carcinogenesis.

In vitro tests showed omega-3 fatty acids induced cell death in malignant and pre-malignant cells at doses which did not affect normal cells, suggesting they have the potential to be used in both the treatment and prevention of certain skin and oral cancers. Omega-3 polyunsaturated fatty acids cannot be made by humans in large quantities and so we must acquire them from our diet.

The scientists were studying a particular type of cancer called squamous-cell carcinoma (SCC). Squamous cells are the main part of the outermost layers of the skin, and SCC is one of the major forms of skin cancer. However, squamous cells also occur in the lining of the digestive tract, lungs, and other areas of the body. Oral squamous cell carcinomas (OSCC) are the sixth most common cancer worldwide and are difficult and very expensive to treat.

In the experiments, the scientists grew cell cultures in the lab from several different cells lines to which they added fatty acids. The cell lines included both malignant oral and skin SCCs, along with pre-malignant cells and normal skin and oral cells. Professor Kenneth Parkinson, Head of the Oral Cancer Research Group at Queen Mary's Institute of Dentistry, said: "We found that the omega-3 fatty acid selectively inhibited the growth of the malignant and pre-malignant cells at doses which did not affect the normal cells.

"Surprisingly, we discovered this was partly due to an over-stimulation of a key growth factor (epidermal growth factor) which triggered cell death. This is a novel mechanism of action of these fatty acids."

While previous research has linked omega-3 fatty acids with the prevention of a number of cancers, there has been very little work done on oral cancers or normal cells.

Dr Zacharoula Nikolakopoulou, carried out the research while studying her PhD at Queen Mary, under the supervision of Professor Parkinson and Professor Adina Michael-Titus, who is co-ordinating a programme of work on the protection of the nervous system with omega-3 fatty acids, in the Centre for Neuroscience and Trauma at Queen Mary's Blizard Institute.

Dr Nikolakopoulou said: "As the doses needed to kill the cancer cells do not affect normal cells, especially with one particular fatty acid we used called Eicosapentaenoic acid (EPA), there is potential for using omega-3 fatty acids in the prevention and treatment of skin and oral cancers.

"It may be that those at an increased risk of such cancers - or their recurrence - could benefit from increased omega-3 fatty acids. Moreover, as the skin and oral cancers are often easily accessible, there is the potential to deliver targeted doses locally via aerosols or gels. However further research is needed to define the appropriate therapeutic doses."

Omega-3 Supplements May Prevent Skin Cancer

Consuming omega-3 fish oils can help to prevent skin cancer, according to the first clinical trial exploring the influence of fish oils on the skin immunity of humans.

The study was conducted by a team of researchers from the University of Manchester and funded by the Association for International Cancer Research, and examined the effect of taking omega-3 on 79 healthy participants.

Findings of the study, published in The American Journal of Clinical Nutrition, revealed that consuming regular doses of fish oils increases immunity to sunlight.

It directly decreases sunlight-induced immunity suppression - called immunosuppression - which affects the body's power to combat skin cancer and infection.

Professor Lesley Rhodes, Professor of Experimental Dermatology from the Photobiology Unit Dermatology Centre at the University's School of Medicine and Salford Royal NHS Foundation Trust, said their study was the first of its kind conducted using humans:

"There has been research in this area carried out on mice in the past but this is the first time that there has been a clinical trial directly in people. It has taken a number of years to get to this stage and the findings are very exciting. This study adds to the evidence that omega-3 is a potential nutrient to protect against skin cancer. Although the changes we found when someone took the oil were small, they suggest that a continuous low level of chemoprevention from taking omega-3 could reduce the risk of skin cancer over an individual's lifetime."

The volunteers consumed a 4g dose of omega-3 - approximately one and a half portions of oily fish each day. Then they were exposed to either 8, 15, or 30 minutes of summer midday sun in Manchester using a specific light machine.

A number of other participants took a placebo before being exposed to the sunlight machine.

Immunosuppression was shown to be 50 percent lower in the subjects that took the omega-3 and were exposed to 8 and 15 minutes of sunshine compared with the volunteers who did not take the supplement. Little to no impact on those in the 30 minute group was shown.

The conclusions from this study are significant in the battle against skin cancer, because earlier studies have always shown that sunscreens are frequently applied incorrectly and only worn on vacation.

However, Professor Rhodes points out omega-3 is not a substitute for suntan lotion or physical protection, and that it should be seen as additional protection factor to help keep the skin from burning.

Historically, fish oil has already been associated with health benefits like protecting against cardiovascular disease, helping prevent age-related vision loss, and even slowing the growth of prostate cancer cells.

Fatty acids found in fish linked to lower risk of breast cancer

A high intake of fatty acids found in fish is associated with a 14% reduction in the risk of breast cancer in later life, finds a study published on bmj.com.

The results show that each 0.1 g per day or 0.1% energy per day increment of intake of n-3 polyunsaturated fatty acid (n-3 PUFA) derived from fish was associated with a 5% reduction in risk. To achieve this risk reduction, intake of oily fish such as salmon, tuna or sardines should be 1-2 portions per person per week.

Breast cancer is one of the most common cancers, accounting for 23% of total cancer cases and 14% of cancer deaths in 2008. Studies suggest that a healthy diet and lifestyle is crucial for the prevention of breast cancer, and dietary fat is one of the most intensively studied dietary factors closely related with risk.

The n-3 PUFAs include ALA, EPA, DPA and DHA. They are involved in chemical messaging in the brain, helping to regulate blood vessel activity and areas of the immune system. The main dietary sources of EPA, DPA and DHA come from oily fish, while ALA is found mainly in nuts, seeds, and leafy green vegetables.

Although n-3 PUFAs are the most promising types of fat to reduce cancer risk, results from human studies are inconsistent.

So a team of researchers based in China set out to investigate the association between fish and n-3 PUFA intake and the risk of breast cancer. Levels were measured from both dietary sources and blood tests.

They reviewed and analysed the results of 26 studies from the United States, Europe and Asia involving over 800,000 participants and over 20,000 cases of breast cancer.

Marine n-3 PUFA was associated with a 14% reduction of breast cancer between the highest and lowest category of marine n-3 PUFA intake. The risk was lowest in Asian populations, probably because fish intake is much higher in Asia than in western countries, say the authors.

Further analysis indicated a dose response: each 0.1 g per day or 0.1% energy per day increment of intake was associated with a 5% reduction in risk. However, no significant protective association was found for ALA - the plant based n-3 PUFA.

The authors say their analysis, together with previous publications, “supports a protective role of marine n-3 PUFA on the incidence of breast cancer.”

They conclude: “Our present study provides solid and robust evidence that marine n-3 PUFA are inversely associated with risk of breast cancer.”

Fish oil may reduce risk of breast cancer

A report in Cancer Epidemiology, Biomarkers & Prevention, (July 2010) a journal of the American Association for Cancer Research, adds to the growing evidence that fish oil supplements may play a role in preventing chronic disease.

Researchers at the Fred Hutchinson Cancer Research Center in Seattle, Wash., led by Emily White, Ph.D., a member of the public health sciences division, asked 35,016 postmenopausal women who did not have a history of breast cancer to complete a 24-page questionnaire about their use of non-vitamin, non-mineral "specialty" supplements in the Vitamins and Lifestyle (VITAL) cohort study.

After six years of follow-up, 880 cases of breast cancer were identified using the Surveillance, Epidemiology and End Results registry.

Regular use of fish oil supplements, which contain high levels of the omega-3 fatty acids, EPA and DHA, was linked with a 32 percent reduced risk of breast cancer. The reduction in risk appeared to be restricted to invasive ductal breast cancer, the most common type of the disease.

The use of other specialty supplements, many of which are commonly taken by women to treat symptoms of menopause, was not associated with breast cancer risk.

This research is the first to demonstrate a link between the use of fish oil supplements and a reduction in breast cancer. Studies of dietary intake of fish or omega-3 fatty acids have not been consistent.

"It may be that the amount of omega-3 fatty acids in fish oil supplements are higher than most people would typically get from their diet," White said.

However, White cautioned against gleaning any recommendations from the results of one study.

"Without confirming studies specifically addressing this," she said, "we should not draw any conclusions about a causal relationship."

Edward Giovannucci, M.D., Sc.D., professor of nutrition and epidemiology at the Harvard School of Public Health and an editorial board member of Cancer Epidemiology, Biomarkers & Prevention, agreed.

"It is very rare that a single study should be used to make a broad recommendation," said Giovannucci. "Over a period of time, as the studies confirm each other, we can start to make recommendations."

Still, fish oil continues to excite many, as evidence emerges about its protective effect on cardiovascular disease and now cancer.

Harvard researchers are currently enrolling patients for the randomized Vitamin D and Omega-3 Trial (also called VITAL), which will assess the impact of fish oil supplements and vitamin D on cancer, heart disease and stroke.

The researchers plan to enroll 20,000 U.S. men aged 60 years and older and women aged 65 years and older who do not have a history of these diseases and have never taken supplements.

Omega-3 fatty acid kills neuroblastoma cancer cells

The next treatment for cancer might come from fish says a new research report published in the March 2010 print edition of the FASEB Journal. In the report, scientists show that the omega-3 fatty acid, "docosahexaenoic acid" or "DHA," and its derivatives in the body kill neuroblastoma cancer cells. This discovery could lead to new treatments for a wide range of cancers, including neuroblastoma, medulloblastoma, colon, breast, and prostate cancers, among others.

"We hope that this study can provide a deeper understanding of the actions of omega-3 fatty acids and their products in cancer cells, and why they can be of such high importance in treatment of the disease," said Helena Gleissman, Ph.D., co-author of the study from the Childhood Cancer Research Unit of the Karolinska Institutet in Stockholm, Sweden. "Ultimately, we hope that we can be able to cure more children with neuroblastoma, and possibly other cancers."

Scientists administered DHA to neuroblastoma cells from the nervous system and analyzed the cells for byproducts as the DHA was metabolized into the cells. Researchers then examined the affect of both DHA and its derivatives on the growth of cancer cells. Results showed that DHA killed the cancer cells, but that the toxic derivatives produced by DHA were even more effective at killing the cancer cells. This suggests that DHA could become a new agent for treating neuroblastoma and possibly many other cancers.

"This is good news for those looking to stop cancer. We now know that DHA plays both offense and defense when it comes to protecting our health," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "It's ability to help prevent numerous diseases is well documented, but now we see that DHA or one of its byproducts might serve as the starting point for a new class of anti-cancer drugs."

Omega-3 Fatty Acids=Reduced Risk of Colon Cancer

Long-chain omega-3 fatty acids, primarily found in fish and seafood, may have a role in colorectal cancer prevention, according to results presented at the American Association for Cancer Research Frontiers in Cancer Prevention Research Conference, 2009.

“Experimental data have shown benefits of long-chain omega-3 fatty acids in colorectal carcinogenesis, ranging from reduced tumor growth, suppression of angiogenesis and inhibition of metastasis,” said Sangmi Kim, Ph.D., a postdoctoral fellow at the National Institute of Environmental Health Sciences, Research Triangle Park, N.C. “Our finding of inverse association between dietary intakes of long-chain omega-3 fatty acids and distal large bowel cancer in white participants adds additional support to the hypothesis.”

Although experimental and clinical data suggest that long-chain omega-3 fatty acids possess anti-neoplastic properties in the colon, epidemiologic data to date has been inconclusive.

Kim and colleagues studied the link between polyunsaturated fatty acid intake and distal large bowel cancer using data from a population-based control study. They recruited 1,509 white participants (716 cancer cases and 787 controls) and 369 black participants (213 cancer cases and 156 controls) using the State Cancer Registry and Division of Motor Vehicles records.

Nineteen polyunsaturated fatty acids were assessed using a validated food frequency questionnaire, which included 124 questions on food items. The researchers used the questionnaire to collect information on the frequency and amount of foods typically consumed in the past 12 months.

Patients who consumed more long-chain omega-3 fatty acids had a reduced risk of distal large bowel cancer. Compared to the lowest quartile, fat intake in the highest quartile was linked with a 39 percent reduced risk of cancer.

The researchers detected these associations in white participants, but not in black participants.

“We were surprised that the association was not also observed among blacks,” Kim said. “We considered several possible explanations but were not able to account for this difference with the data we had. This finding warrants future study, but we should be careful about drawing conclusions about potential racial differences in the benefit from long-chain omega-3 fatty acids from this study.”

“An increase in dietary intake of long-chain omega-3 fatty acids, which mainly come from fish and seafood, may be beneficial in the prevention of distal large bowel cancer,” Kim said.

Fatty acids could aid cancer prevention and treatment

Omega-3 fatty acids, contained in oily fish such as salmon and trout, selectively inhibit growth and induce cell death in early and late-stage oral and skin cancers, according to new research from scientists at Queen Mary, University of London published online in the journal Carcinogenesis.

In vitro tests showed omega-3 fatty acids induced cell death in malignant and pre-malignant cells at doses which did not affect normal cells, suggesting they have the potential to be used in both the treatment and prevention of certain skin and oral cancers. Omega-3 polyunsaturated fatty acids cannot be made by humans in large quantities and so we must acquire them from our diet.

The scientists were studying a particular type of cancer called squamous-cell carcinoma (SCC). Squamous cells are the main part of the outermost layers of the skin, and SCC is one of the major forms of skin cancer. However, squamous cells also occur in the lining of the digestive tract, lungs, and other areas of the body. Oral squamous cell carcinomas (OSCC) are the sixth most common cancer worldwide and are difficult and very expensive to treat.

In the experiments, the scientists grew cell cultures in the lab from several different cells lines to which they added fatty acids. The cell lines included both malignant oral and skin SCCs, along with pre-malignant cells and normal skin and oral cells. Professor Kenneth Parkinson, Head of the Oral Cancer Research Group at Queen Mary's Institute of Dentistry, said: "We found that the omega-3 fatty acid selectively inhibited the growth of the malignant and pre-malignant cells at doses which did not affect the normal cells.

"Surprisingly, we discovered this was partly due to an over-stimulation of a key growth factor (epidermal growth factor) which triggered cell death. This is a novel mechanism of action of these fatty acids."

While previous research has linked omega-3 fatty acids with the prevention of a number of cancers, there has been very little work done on oral cancers or normal cells.

Dr Zacharoula Nikolakopoulou, carried out the research while studying her PhD at Queen Mary, under the supervision of Professor Parkinson and Professor Adina Michael-Titus, who is co-ordinating a programme of work on the protection of the nervous system with omega-3 fatty acids, in the Centre for Neuroscience and Trauma at Queen Mary's Blizard Institute.

Dr Nikolakopoulou said: "As the doses needed to kill the cancer cells do not affect normal cells, especially with one particular fatty acid we used called Eicosapentaenoic acid (EPA), there is potential for using omega-3 fatty acids in the prevention and treatment of skin and oral cancers.

"It may be that those at an increased risk of such cancers - or their recurrence - could benefit from increased omega-3 fatty acids. Moreover, as the skin and oral cancers are often easily accessible, there is the potential to deliver targeted doses locally via aerosols or gels. However further research is needed to define the appropriate therapeutic doses."

Omega-3 fatty acids more effective at inhibiting growth of triple-negative breast cancer

Researchers from Fox Chase Cancer Center have found that omega-3 fatty acids and their metabolite products slow or stop the proliferation, or growth in the number of cells, of triple-negative breast cancer cells more effectively than cells from luminal types of the disease. The omega-3s worked against all types of cancerous cells, but the effect was observed to be stronger in triple-negative cell lines, reducing proliferation by as much as 90 percent. The findings were presented at the AACR Annual Meeting 2013.

Omega-3 fatty acids are found in oily fish like sardines and salmon, and also in oils derived from plants like hemp and flax. Previous studies suggest these compounds can negatively affect critical mechanisms in cancer cells, namely those responsible for proliferation and for apoptosis, or programmed cell death. Lead author on the study Thomas J. Pogash, a scientific technician in the Fox Chase Cancer Center lab of Jose Russo, MD, says the new work underscores the important role common compounds found in food may play in keeping cancer at bay.

"Diet can play a critical role in breast cancer prevention," says Pogash. "When you compare a western diet to a mediterranean diet, which has more omega-3s, you see less cancer in the mediterranean diet. They eat much more fish."

Breast cancer is a heterogeneous group of cancers comprising diseases that differ on the molecular level. Patients with different types of breast cancer respond differently to treatments. Four distinct categories of the disease are generally recognized. Two of those, luminal A and luminal B, grow in the luminal cells that line milk ducts in the breast and have receptors for estrogen and progesterone (prognosis is generally better for patients with luminal A than with luminal B). A third category includes tumors that test positive for the HER2 receptor.

Tumors in the fourth category, triple-negative, lack receptors for progesterone, estrogen, and a protein called HER2/neu. As a result, this type of disease is insensitive to treatments like trastuzumab, which disrupts the HER2 receptor, and tamoxifen, which targets the estrogen receptor.

Russo notes that no targeted therapies are currently available for patients diagnosed with triple-negative breast cancer. Combination chemotherapies are the standard of care for early-stage disease.

"This type of cancer, which is found more frequently in Latina and African-American women, is highly aggressive and has a low survival rate," says Russo. "There is not any specific treatment for it."

When a cancer cell digests omega-3s, the fatty acid is broken down into smaller molecules called metabolites. Russo, Pogash, and their colleagues tested the effect of large omega-3 parent molecules, as well as their smaller metabolic derivatives, on three luminal cell lines and seven lines that included basal-type triple-negative cells.

Omega-3 and its metabolites were observed to inhibit proliferation in all cell lines, but the effect was dramatically more pronounced in the triple-negative cell lines. In addition, the metabolites of omega-3 reduced the motility, or ability to move, by 20-60 percent in the triple-negative basal cell lines.

This study is part of a consortium between Fox Chase Cancer Center and Pennsylvania State University under a five-year grant awarded by the Komen Foundation. Russo is the principal investigator of the project at Fox Chase. Andrea Manni, MD, leader of the Pennsylvania State University team, has extended this work to animal models, studying the anticancer effects of omega-3s and its metabolites on mouse models of triple-negative breast cancer.

Russo and his colleagues are working on two related projects, one on the role of epigenetic events in the mechanism of cell transformation and another on the potential action of peptides of the hormone human chorionic gonadotropin (hCG) on breast cancer prevention.