Δ 12-prostaglandin J 3, an omega-3 fatty acid-derived metabolite, selectively ablates leukemia stem cells in mice

Shailaja Hegde, Naveen Kaushal, Kodihalli C. Ravindra, Christopher Chiaro, Kelsey T. Hafer, Ujjawal H. Gandhi, Jerry T. Thompson, John P. Van Den Heuvel, Mary J. Kennett, Pamela Hankey, Robert F. Paulson, K. Sandeep Prabhu

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Targeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that Δ 12-PGJ 3, a novel and naturally produced CyPG from the dietary fish-oil ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the development of leukemia in 2 well-studied murine models of leukemia. IP administration of Δ 12-PGJ 3 to mice infected with Friend erythroleukemia virus or those expressing the chronic myelogenous leukemia oncoprotein BCRABL in the hematopoietic stem cell pool completely restored normal hematologic parameters, splenic histology, and enhanced survival. More importantly, Δ 12-PGJ 3 selectively targeted leukemia stem cells (LSCs) for apoptosis in the spleen and BM. This treatment completely eradicated LSCs in vivo, as demonstrated by the inability of donor cells from treated mice to cause leukemia in secondary transplantations. Given the potency of ω-3 polyunsaturated fatty acid-derived CyPGs and the well-known refractoriness of LSCs to currently used clinical agents, Δ 12- PGJ 3 may represent a new chemotherapeutic for leukemia that targets LSCs.

Original languageEnglish (US)
Pages (from-to)6909-6919
Number of pages11
JournalBlood
Volume118
Issue number26
DOIs
StatePublished - Dec 22 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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