Omega-3 Fatty Acids Found to Suppress Liver Cancer

The two studies were presented in early April 2006 at the annual meeting of the American Association for Cancer Research (AACR), held in Washington (D.C., USA), and suggest that omega-3 fatty acids may be an effective therapy for both the treatment and prevention of human liver cancers.

The first study examined the effect and processes of omega-3 and omega-6 polyunsaturated fatty acids in human hepatocellular carcinoma cells. Hepatocellular carcinoma accounts for 80-90% of all liver cancers and is typically fatal within three to six months of diagnosis.

It has been known for some time that omega-3 fatty acids can inhibit certain cancer cells. So, we were interested in determining whether these substances could inhibit liver cancer cells. If so, we also wanted to know by what mechanism this inhibition occurs, said Tong Wu, M.D., Ph.D., from the division of transplantation pathology, University of Pittsburgh School of Medicine (PA, USA), in whose laboratory the studies were performed.

The researchers treated the hepatocellular carcinoma cells with either the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or the omega-6 fatty acid arachidonic acid (AA), for 12 to 48 hours. DHA and EPA treatment resulted in a dose-dependent suppression of cell growth, while AA treatment demonstrated no significant effect.

According to the investigators, the effect of omega-3 fatty acids on cancer cells probably is caused by the induction of apoptosis, or programmed cell death. Indeed, the investigators found that DHA treatment induced the splitting up, or cleavage, of an enzyme in the cell nucleus known as poly (ADP-Ribose) polymerase (PARP), which is involved in repairing DNA damage, mediating apoptosis, and regulating immune response. The cleavage of this enzyme is thought to be a known indicator of apoptosis. Moreover, DHA and EPA treatment indirectly reduced the levels of another protein known as beta-catenin, an overabundance of which has been associated with the development of various tumors.

Beta-catenin is known to promote cell growth and also is implicated in tumor cell promotion. Therefore, our finding that omega-3 fatty acids can decrease levels of beta-catenin is further evidence that these compounds have the ability to interact on several points of pathways involved in tumor progression, explained Dr. Wu.

In the second study, the investigators treated cholangiocarcinoma tumor cells with omega-3 and omega-6 fatty acids for 12 to 48 hours. Cholangiocarcinoma is an especially aggressive form of liver cancer that starts in the ducts that carry bile from the liver and has an extremely high mortality rate. Once more, the omega-3 fatty acids DHA and EPA treatments resulted in a dose-dependent inhibition of cancer cell growth, while the omega-6 fatty acid AA treatment had no significant effect. Similarly, DHA treatment triggered a cleavage form of PARP in cholangiocarcinoma cells, and DHA and EPA treatment considerably decreased the level of beta-catenin protein in the cells.

According to Dr. Wu, these results suggest that omega-3 fatty acids not only may be a successful therapy for the treatment of human liver cancers but may also be a way of protecting the liver from steatohepatitis, a chronic liver disease typified by the accumulation of fat in the liver and considered to be a precursor of hepatocellular carcinoma. The next step in the process, he said, is to examine the effects of omega-3 fatty acids in mice harboring human liver tumors.


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