Study Title:

DHA Kills Cancer Cells

Study Abstract

Docosahexaenoic acid (DHA) protects neural cells from stress-induced apoptosis. On the contrary, DHA exerts anticancer effects, and we have shown that DHA induces apoptosis in neuroblastoma, an embryonal tumor of the sympathetic nervous system. We now investigate the DHA metabolome in neuroblastoma using a targeted lipidomic approach in order to elucidate the mechanisms behind the DHA-induced cytotoxicity. LC-MS/MS analysis was used to identify DHA-derived lipid mediators in neuroblastoma cells. Presence of the 15-lipoxygenase enzyme was investigated using immunoblotting, and cytotoxic potency of DHA and DHA-derived compounds was compared using the MTT cell viability assay. Neuroblastoma cells metabolized DHA to 17-hydroxydocosahexaenoic acid (17-HDHA) via 17-hydroperoxydocosahexaenoic acid (17-HpDHA) through 15-lipoxygenase and autoxidation. In contrast to normal neural cells, neuroblastoma cells did not produce the anti-inflammatory and protective lipid mediators, resolvins and protectins. 17-HpDHA had significant cytotoxic potency, with an IC50 of 3–6 µM at 72 h, compared to 12–15 µM for DHA. -Tocopherol protected cells from 17-HpDHA-induced cytotoxicity. DHA inhibited secretion of prostaglandin-E2 and augmented the cytotoxic potency of the cyclooxygenase-2-inhibitor celecoxib. The cytotoxic effect of DHA in neuroblastoma is mediated through production of hydroperoxy fatty acids that accumulate to toxic intracellular levels with restricted production of its products, resolvins and protectins.

From press release:

The next treatment for cancer might come from fish says a new research report published in the March 2010 print edition of the FASEB Journal. In the report, scientists show that the omega-3 fatty acid, "docosahexaenoic acid" or "DHA," and its derivatives in the body kill neuroblastoma cancer cells. This discovery could lead to new treatments for a wide range of cancers, including neuroblastoma, medulloblastoma, colon, breast, and prostate cancers, among others.

"We hope that this study can provide a deeper understanding of the actions of omega-3 fatty acids and their products in cancer cells, and why they can be of such high importance in treatment of the disease," said Helena Gleissman, Ph.D., co-author of the study from the Childhood Cancer Research Unit of the Karolinska Institutet in Stockholm, Sweden. "Ultimately, we hope that we can be able to cure more children with neuroblastoma, and possibly other cancers."

Scientists administered DHA to neuroblastoma cells from the nervous system and analyzed the cells for byproducts as the DHA was metabolized into the cells. Researchers then examined the affect of both DHA and its derivatives on the growth of cancer cells. Results showed that DHA killed the cancer cells, but that the toxic derivatives produced by DHA were even more effective at killing the cancer cells. This suggests that DHA could become a new agent for treating neuroblastoma and possibly many other cancers.

"This is good news for those looking to stop cancer. We now know that DHA plays both offense and defense when it comes to protecting our health," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "It's ability to help prevent numerous diseases is well documented, but now we see that DHA or one of its byproducts might serve as the starting point for a new class of anti-cancer drugs."

Study Information

Helena Gleissman, Rong Yang, Kimberly Martinod, Magnus Lindskog, Charles N. Serhan, John Inge Johnsen, and Per Kogner
Docosahexaenoic acid metabolome in neural tumors: identification of cytotoxic intermediates.
FASEB Journal,
2010 March
Childhood Cancer Research Unit of the Karolinska Institutet in Stockholm, Sweden.

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