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Harnessing fatty acids to fight cancer.

Harnessing fatty acids to fight cancer

Fatty acids are straight-chain, carbon-based molecules that are among the building blocks of fats and oils. Three polyunsaturated ones -- linoleic, gamma-linolenic (GLA) and arachidonic (AA)--are even essential nutrients. Bur cancer cells are deficient polyunsaturated fatty acids (PUFAs). In fact, says Michel Begin, "they do everything they can to get rid of them." And that led Begin and his Canadian colleagues at the private Efamol Research Institute in Kentville, Nova Scotia, to explore the tumor/PUFA relationship. Three years ago they reported that PUFAs could kill tumor cells. Now they have identified not only which are the most efficient tumor-cell killers, but also their modus operandi. Begin presented their findings last week at the American Oil Chemists' Society annual meeting in Phoenix, Ariz.

Working with cultured human breast-cancer cells, the Canadian researchers found that while AA, EPA (eicosapentanoic acid) and GLA were about equally effective in killing tumor cells -- and were the most lethal of the seven PUFAs being looked at -- their effect on normal cells differed dramatically. EPA, for example, was just about as lethal to normal cells. AA was not quite as toxic to normal cells, but it also wasn't benign. At concentrations of about 0.5 nanogram per cultured cell, however, GLA was quite deadly to tumor cells and innocuous to healthy ones.

Because PUFAs are very susceptible to oxidizing reactions, their presence in cell membranes can easily cause serious cell damage. In search of the mechanism for PUFA-initiated tumor-cell killing, Begin, Greg Ells and David Horrobin focused on damaging oxygen-based reactions. Their results, first described in the April 6 JOURNAL OF THE NATIONAL CANCER INSTITUTE, suggest the cell killing by GLA and other PUFAs correlates with their generation of superoxide radicals (highly reactive oxygen molecules) and toxic secondary products -- primarily singlet oxygen, aldehydes and polymers of peroxides.

Though the GLA concentration needed to kill cultured cancer cells is small, Begin says it is still at least 5 times higher than that normally found in the body. So he and his coworkers turned to transition metals -- like iron and copper -- to see if they could enhance GLA's efficacy. As Begin explains, these metals increase the degradation products of hydroperoxides, reactive chemicals active in this PUFA-initiated tumor-cell killing. the researchers found that adding just 10 micrograms of iron per milliliter of culture medium was sufficient to halve the dose of GLA that killed tumor cells. Alternatively, doubling the iron concentration would double or triple the rate of call killing.

What this suggests, Begin says, is that with sufficient iron, it might be possible to trigger the body to kill its own tumor cells--just using the GLA naturally present. The trick, and one Begin is already at work to engineer in animals and humans, is seeing that the iron and appropriate fatty acids both enter the tumor cells.
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Publication:Science News
Date:May 21, 1988
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