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- Investigators report one mechanism by which omega-3 reduces metastatic melanoma
- News - People with epilepsy tend to have low levels of DHA, supplementation may help
Denkins Y, Kempf D, et al. Role of omega-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma. J. Lipid Research, 2005; 46: 1278-1284.
Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that omega-6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation.
We investigated the effects of omega-3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice.
We show that 1) tumor necrosis factor-alpha upregulates the expression of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2) omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2 production. AA increased COX-2 mRNA expression and prostaglandin production in omega-6-stimulated 70W cells.
Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased MatrigelTM invasion 2.4-fold, whereas EPA or DHA did not.
Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas exposure to PGE3 significantly decreased invasion.
Our results demonstrate that incubation of 70W cells with either AA or PGE2 increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in MatrigelTM invasion.
Taken together, these results indicate that omega-3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.
Omega-3 fatty acids have been associated with numerous health benefits, from brain development and preventing memory loss to suppressing tumours and cutting heart disease.
But according to new findings in the US, one particular fatty acid, docosahexaenoic acid (DHA), is found at abnormally low levels in patients with uncontrolled epilepsy, suggesting DHA supplementation in the diet could potentially help control seizures.
Demand for omega-3 fatty acids notably found in fish - has surged in recent months on the back of increasing scientific evidence for the benefits to consumer health.
DHA is essential for the development of the nervous system and visual abilities in babies and for the proper functioning of the brain in adults. The human body cannot produce sufficient amounts of DHA for the needs of the eye and brain consequently it must be consumed through foods, such as cold water fatty fish, or in supplemental form.
The small US study, carried out by researchers at Emory University School of Medicine, was based on 41 people with Orefractory complex partial seizures¹ - a common type of seizure that develops in one brain region and is resistant to antiepileptic medication - compared to a control group of 57 healthy participants.
Both groups had blood drawn and analysed for levels of DHA. After complete analyses, the researchers report that they found Osignificantly lower levels of DHA¹ in the red blood cell membranes of the group with uncontrolled epilepsy - 2.74 per cent - when compared to DHA levels in the healthy group - 3.46 per cent.
"By determining a deficiency in the red blood cell membranes in these patients, we infer that brain cell membranes are also depleted of this normal fatty acid," said researcher Dr.Thomas Henry at Emory. "Future studies are needed to determine if DHA supplementation can help control seizures in this patient population," he concluded.
According to the World Health Organisation, it is likely that around 50 million people in the world have epilepsy at any one time. The lifetime prevalence of epilepsy - the number of people presently in the world who have epilepsy now or have had it in the past or will experience it in the future - is approximately 100 million people.
The results of the study was presented at the American Academy of Neurology last week in San Francisco.
