To the editor:
We read with great interest the article by Hedge et al,1 reporting that Δ12-prostaglandin (PG) J3 (Δ12-PGJ3) has antileukemic activity in mice. Anti-inflammatory and antineoplastic activity has also been reported for 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2).2 We agree with Hedge et al1 that one of the most important questions is whether sufficient quantities of Δ12-PGJ3 are formed in vivo to exert any biologic activity. Here, we comment on this eminently crucial issue from pharmacologic and nutrition perspectives.
PGJ3 and PGJ2 are the dehydrated products of PGD3 and PGD2 formed in vivo from eicosapentaenoic acid (EPA) and arachidonic acid (ARA), respectively, by the catalytic action of cyclooxygenase (COX). PGJ3 and PGJ2 are further dehydrated and isomerized to produce Δ12-PGJ3 and 15d-PGJ3 and 5d-PGJ2, respectively. Common feature of Δ12-PGJ3 and 15d-PGJ2 is the highly reactive cyclopentenone ring, which is readily attacked by low- and high-molecular-mass thiols to form thioethers (Figure 1). Thiolation of Δ12-PGJ3 and 15d-PGJ2 is likely to reduce both availability and bioactivity of Δ12-PGJ3 and 15d-PGJ2. So far, there are no data about excretion of Δ12-PGJ3 and 15d-PGJ3. We (Figure 1) and others3 found only pM-concentrations of 15d-PGJ2 in human urine, while PGJ3 metabolites including 15d-PGJ3 were below the detection limit of our method (30 pM) in urine. This may suggest that basal PGJ3 biosynthesis from EPA is several fold lower than PGJ2 from ARA. Dietary EPA has been shown to increase formation of prostaglandin I3 (PGI3) and thromboxane A3 (TxA3), but EPA, even at very high doses, did not increase PGI3 and TxA3 synthesis to a degree comparable with that of PGI2 and TxA2 from ARA.4
Δ12-PGJ3 and 15d-PGJ2 are considered potentially useful therapeutic agents for the treatment of cancer.1,2 Dietary EPA supplementation is unlikely to produce nM-concentrations of Δ12-PGJ3 required for antileukemic activity, but topical administration of considerable amounts of synthetic Δ12-PGJ3 would be required.
Acknowledgments: The authors thank B. Beckmann, K. Berg, A. Mitschke and M.-T. Suchy for laboratory assistance and Frank-Mathias Gutzki for performing GC-MS/MS analyses.
Contribution: D.T. and D.O.S designed and performed the study, analyzed the data, and wrote the manuscript.
Conflict-of-interest disclosure: The authors declare no competing financial interests.
Correspondence: Prof Dimitrios Tsikas, Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany; e-mail: firstname.lastname@example.org.