Δ12-prostaglandin J3, an omega-3 fatty acid-derived metabolite, selectively ablates leukemia stem cells in mice
Menée sur un modèle murin, cette étude montre que la delta-12-prostaglandine -J3, un métabolite dérivé des acides gras oméga 3, peut induire de manière sélective l'apoptose des cellules souches leucémiques dans la rate et la moelle osseuse
Targeting cancer stem cells (CSC) is of paramount importance to successfully combat the relapse of cancer. Recently, in silico screen of public gene expression datasets identified cyclooxygenase- derived cyclopentenone prostaglandins (CyPG) as likely agents to target malignant stem cells. We show here that Δ12-PGJ3, a novel and naturally produced CyPG from the dietary fish-oil omega-3 polyunsaturated fatty acid (n-3 PUFA), eicosapentaenoic acid (EPA; 20:5), alleviates the development of leukemia in two well-studied murine models of leukemia. Intraperitoneal administration of Δ12-PGJ3 to mice infected with Friend erythroleukemia virus (FV) or those expressing chronic myelogenous leukemia (CML) oncoprotein BCR-ABL in the hematopoietic stem cell (HSC) pool completely restored normal hematological parameters, splenic histology, and enhanced the survival of such mice. More importantly, Δ12-PGJ3 selectively targeted leukemia stem cells (LSC) for apoptosis in the spleen and bone marrow. This treatment completely eradicated leukemia stem cells in vivo as demonstrated by the inability of donor cells from treated mice to cause leukemia in secondary transplants. Given the potency of n-3 PUFA-derived CyPG and the well-known refractoriness of LSC to currently used clinical agents, Δ12-PGJ3 may represent a new chemotherapeutic for leukemia that targets LSCs.