Candidate Fish Oil Drug Eliminates Leukemia Stem Cells in Mouse Model

To cure a patient of cancer, a drug regimen must prevent relapse by eliminating residual cancer stem cells, which are usually resistant to chemotherapy.

A computer search of public gene-expression datasets for agents able to target malignant stem cells identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely candidates.

Investigators at Pennsylvania State University (University Park, PA, USA) evaluated the efficacy of one of these compounds in a mouse leukemia model. The compound, delta-12-PGJ3, is a novel and naturally produced CyPG from the dietary fish-oil omega-3 polyunsaturated fatty acid eicosapentaenoic acid.

The Investigators reported in the December 22, 2011, issue of the journal Blood that they injected 600 ng of delta-12-PGJ3 each day for a week into mice with chronic myelogenous leukemia (CML). At the end of the week, the animals’ blood counts were normal and their spleens had returned to normal size. Significantly, delta-12-PGJ3 selectively targeted leukemia stem cells (LSCs) for apoptosis in the animals’ spleens and bone marrow. This treatment completely eradicated LSCs in vivo, as demonstrated by the inability of donor cells from treated mice to cause leukemia in secondary transplantations.

At the molecular level, delta-12-PGJ3 was shown to activate the p53 tumor suppressor gene, which caused apoptosis in the leukemia stem cells.

“Research in the past on fatty acids has shown the health benefits of fatty acids on cardiovascular system and brain development, particularly in infants, but we have shown that some metabolites of omega-3 have the ability to selectively kill the leukemia-causing stem cells in mice,” said senior author Dr. Sandeep Prabhu, associate professor of immunology and molecular toxicology at Pennsylvania State University. “The important thing is that the mice were completely cured of leukemia with no relapse.”

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