Omega-3 offers hope for cancer drugs

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New anti-breast cancer drugs could be developed after latest
research suggested that Omega-3, a fatty acid found in oily fish,
could be combined with an anaesthetic to reduce the ability of
breast cancer cells to develop into malignant tumours.

In the journal Breast Cancer Research, scientists discovered that compounds of Omega-3 fatty acids and the anaesthetic, propofol, inhibited cancer cell migration by 50 per cent, significantly reducing metastatic activity. These new compounds could open up the possibility of being developed into a new family of anti-cancer drugs.

Omega-3 fatty acids, like those found in oily fish such as tuna, salmon, herring, sardines and mackerel, are known to have many positive health benefits, commonly recommended for maintaining a healthy heart.

The properties of Omega 3 are known to reduce cholesterol levels and help prevent cardiovascular disease. Research suggests that Omega-3 may also protect against arthritis, lupus, and asthma and help people with biopolar disorder.

Lead researcher Dr Rafat Siddiqui and colleagues, from the Methodist Research Institute and Indiana University​ in Indianapolis, studied the effects of two particular types of Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

Omega-3 fatty acids such as DHA and EPA have a minimal effect on cancer cells when applied alone. However, when propofol - a potent anti-oxidant known to inhibit cancer cell migration by 5-10 per cent, was combined with DHA or EPA the conjugates inhibited cancer cell adhesion by 15 per cent and 30 per cent respectively, reducing cell migration by 50 per cent and increased apoptosis by 40 per cent.

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

Propofol (2,6 diisopropylphenol) is the most extensively used general anaesthetic sedative agent employed today and is non-toxic to humans even at high levels (3 to 8 µg/ml; 20 to 50 µM).

The researchers mentioned that clinically relevant concentrations of propofol (3 to 8 µg/ml) were reported to decrease the metastatic potential of human cancer cells, including HeLa, HT1080, HOS and RPMI-7951 cells.

Siddiqui and his colleagues postulated that DHA and EPA might have a unique effect on propofol. "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,"​ they commented.

Often a major obstacle to the successful use of a drug is its ability to be taken up and retained by cells. Either the drug must have its target on the outer membrane surface or it must cross the plasma membrane through either an existing transport system or by simple diffusion to affect intracellular targets.

One approach to overcoming the problem of cell entry and retention has been to link water-soluble drugs to lipophilic carriers. Several attempts have been made in the past to synthesise novel compounds by conjugating fatty acids with drugs.

Previous studies, in which chlorambucil-fatty acid conjugates (Chlfatty acid) were synthesised and tested on human lymphoma cell lines, found the conjugates (including those with DHA) selectively affected neoplastic lymphocytes, with minimal effect on quiescent lymphocytes.

The cell toxicity observed with Chl-arachidonic acid and Chldocosahexaenoic acid against lymphoma cells was equal to or higher than the individual toxic potential of either chlorambucil or the fatty acids, whereas the Chl-oleic acid conjugate was much less toxic than Chl alone.

The authors concluded that the coupling of chlorambucil with polyunsaturated fatty acids was selective against neoplastic versus quiescent lymphocytes.

Indeed, the authors of this study​ said that it may be possible that propofol conjugated with arachidonic acid, an omega-6 polyunsaturated fatty acid, or with a saturated fatty acid might be just as effective.

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