Omega-3 Fatty Acids Inhibit Growth Of Liver Cancer Cells

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Article 07 Apr 2006 - 4:00am (UK)

 

Two new studies by a University of Pittsburgh research team suggest

that omega-3 fatty acids--substances that are found in high

concentrations in fish oils and certain seeds and nuts--significantly

inhibit the growth of liver cancer cells. The studies, presented

today at the annual meeting of the American Association for Cancer

Research (AACR), at the Washington Convention Center in Washington,

D.C., suggest that omega-3 fatty acids may be an effective therapy

for both the treatment and prevention of human liver cancers.

 

The first study, Abstract number 2679, looked at the effect and

mechanism of omega-3 and omega-6 polyunsaturated fatty acids in human

hepatocellular carcinoma cells. Hepatocellular carcinoma accounts for

80 to 90 percent of all liver cancers and is usually 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., a member of the division of transplantation

pathology, University of Pittsburgh School of Medicine, in whose

laboratory the research was conducted.

 

The investigators 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 inhibition of cell growth, whereas AA treatment

exhibited no significant effect.

 

According to the investigators, the effect of omega-3 fatty acids on

cancer cells likely is due to 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, or PARP, which is

involved in repairing DNA damage, mediating apoptosis and regulating

immune response. The cleavage of this enzyme is considered a tell-

tale indicator of apoptosis. Furthermore, DHA and EPA treatment

indirectly decreased the levels of another protein known as beta-

catenin, an overabundance of which has been linked to 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, Abstract number 2680, the investigators treated

cholangiocarcinoma tumor cells with omega-3 and omega-6 fatty acids

for 12 to 48 hours. Cholangiocarcinoma is a particularly aggressive

form of liver cancer that arises in the ducts that carry bile from

the liver and has an extremely high mortality rate. Again, 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. Likewise, DHA treatment induced

a cleavage form of PARP in cholangiocarcinoma cells, and DHA and EPA

treatment significantly decreased the level of beta-catenin protein

in the cells.

 

According to Dr. Wu, these findings suggest that omega-3 fatty acids

not only may be an effective therapy for the treatment of human liver

cancers but may also be a means of protecting the liver from

steatohepatitis, a chronic liver disease characterized by the buildup

of fat in the liver and believed to be a precursor of hepatocellular

carcinoma. The next step in the process, he said, is to test the

effects of omega-3 fatty acids in mice harboring human liver tumors.

 

###

 

This work was supported by grants from the National Cancer Institute.

Kyu Lim, Ph.D., in Dr. Wu's laboratory performed the major

experiments. Other investigators involved in these studies include

Chang Han, Ph.D., and Lihong Xu, Ph.D., all from the University of

Pittsburgh.

 

Contact: Jim Swyers

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Clare Collins

CollCX

 

University of Pittsburgh Medical Center