Neural cancer (neuroblastoma) in young children is the most common solid tumour form in this age group. The prognosis is very poor and some 40 per cent of patients die of the disease. However, it is known that fatty acids can protect healthy nerve cells from dying, and at the same time kill several types of cancer cells. In the current study, the scientists were interested in exploring what happens to DHA, an Omega-3 fatty acid found mainly in oily fish (e.g. salmon and mackerel), inside the cancer cell.
Using an advanced method called liquid chromatography combined with mass spectrometry, the researchers looked at the products that were formed on the breakdown of DHA and which of them have a lethal effect on the cancer cell. They also tried to identify the enzymes involved in the breakdown process.
“We observed that DHA forms hydroperoxy fatty acids and hydroxy fatty acids inside the cancer cell,” says Helena Gleissman, researcher at Karolinska Institutet and the study´s principal author. “These fatty acids are oxidised through the agency of enzymes called 5- and 15-lipoxygenase, but they can also be oxidised spontaneously. Hydroperoxy fatty acids are particularly involved in apoptosis.”
DHA can be converted into these cell-killing oxidised fatty acids in healthy neurons, but they are then converted further into substances called resolvins and protectins, thus avoiding the accumulation of cytolethal oxidised fatty acids in the cell. Protectins are particularly effective at protecting nerve cells from dying, which from a future treatment perspective makes it especially interesting that neither resolvins nor protectins are formed in neuroblastoma cells.
“While DHA kills cancer cells in the nervous system via hydroperoxy fatty acids, it protects healthy nerve cells from dying via protectins,” says Dr Gleissman. “If we can find a way of controlling this process, there is a good chance that DHA can serve as both sword and shield in neuroblastoma patients and act as a complement to cytostatic therapy.”
The study was based on a collaboration between Professor Per Kogner´s research group at Karolinska Institutet and Professor Charles N Serhan´s group at Harvard Medical School. The researchers will now be looking into how DHA can be applied most effectively in the treatment of cancer. The research was funded by the Swedish Children´s Cancer Foundation, Swedish Research Council, Swedish Cancer Society, Erik and Edith Fernström´s Foundation for Medical Research, Cystic Fibrosis Foundation, and NIH.
Docosahexaenoic acid metabolome in neural tumors: identification of cytotoxic intermediates
The FASEB Journal, print issue March 2010
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