Endogenous levels of D12-PGJ3 derived from eicosapentaenoic acid

摘要

In response to the comment by Tsikas and Stichtenoth, we would like to provide clarification for their views and address the questions. First, while it is correct that the reactivity of the 2 electrophilic centers could make these classes of compounds less bioavailable, our data clearly demonstrates that intraperitoneal administration of D12-PGJ3 completely eradicates leukemia stem cells in the bone marrow and spleen. This suggests that the formation of Michael adducts does not affect their antileukemic activity nor systemic bioavailability. Second, it is not surprising to find that the pm concentrations of 2- and 3-series CyPGs (of the J class) in the urine. Our studies show (see Figure 1 in Hegde et al) that macrophages cultured with 50 muM EPA for a week, produce D12-PGJ3 in the cell culture media in quantities (nM) sufficient to target leukemia stem cells.