Hepatocellular carcinoma (HCC) or liver cancer might have finally been met with an agent that blocks its growth and isn’t harmful to human health. Docosahexaenoic acid (DHA), an ω-3 fatty acid, was used by researchers of Anhui Province, China to stop the migration of and induce apoptosis in hepatocellular carcinoma cells.
Epidemiologically, liver cell cancer usually affects more men than women, those over the age of 50, and people in Asia and Africa and is usually caused by alcohol abuse, chronic liver inflammation, or hepatitis B/C infection.
Omega (ω) 3 fatty acids are commonly found in fish oils and known to have beneficial effects for the body. An example is the incidence of breast cancer being four to five times higher in western countries than in Japan, a country that eats much more seafood daily than the west. DHA specifically was used in this study to test the effects of ω-3 polyunsaturated fatty acids on HCC and search for the mechanism of action.
HCC cells were cultured then treated with varying levels of DHA for 72 hours. Using between 25 and 200 µmol/L DHA an increasing trend of decreased cell density was seen between time 0 and 72 hours.(so, less cells with more DHA and time). After treating HCC cell cultures for 72 hours with 200 µmol/L DHA the following was seen:
– Just over 20% of cancer cells survived
– An over 30 fold increase in apoptosis (cell suicide) was seen
The pathway behind the significant increase in cell apoptosis was attributed to modified activity of the Bim gene, Bcl-2 protein, Bax protein, and caspase-3 protein effector. Bcl-2 and Bim, two factors that protect cells against apoptosis, both showed decreased activity with increasing DHA. Also, caspase-3 and Bax, two pro-apoptotic factors, showed increased activity.
Finally, a scratch wound assay testing how quickly HCC cells migrated to the wound in the presence/absence of DHA showed blunted migration of cells when DHA was included. Immunofluorescence showed decreased MMP-9, a protein required for HCC cell migration, levels based on DHA concentration.
Wrapping all together, the modified Bim, Bcl-2, caspase-3, and Bax levels showing increased apoptosis, decreased MMP-9 levels indicating less cell migration, and overall decreased cell density seen with more DHA used yields significant evidence for DHA being effective in stopping liver cancer.
Since DHA is an ω-3 and essential fatty acid, it may be a shorter task to move it into the clinic as a treatment for hepatocellular carcinoma.
Si-Nan Sun, Wei-Dong Jia, Hao Chen, Jin-Liang Ma, Yong-Sheng Ge, Ji-Hai Yu, Jian-Sheng Li. Docosahexaenoic acid (DHA) induces apoptosis in human hepatocellular carcinoma cells. International Journal of Clinical and Experimental Pathology, 2013.