delta 12-Prostaglandin J2, an ultimate metabolite of prostaglandin D2 exerting cell growth inhibition

L-1210 murine leukemia cells were exposed to prostaglandin D2 (PGD2), 10 micrograms/ml, in culture medium for various time, and subsequent cell growth was observed. More than 24 h exposure to PGD2 was required to inhibit cell growth almost completely. During this period, PGD2 degraded time-dependently into several products. The major product was identified as delta 12-PGJ2 by TLC, UV and mass spectra. When delta 12-PGJ2 was added to cells instead of PGD2, it evoked growth inhibition with much shorter contact time than PGD2. In addition, when the medium containing PGD2 was preincubated at 37 degrees C for 24 h, it elicited growth inhibition with only 6 h contact with cells. Furthermore, when the medium containing PGD2 was changed every 6 h during 24 h exposure time to cells, no significant growth inhibition was observed. These results suggested that PGD2 per se has little, if any, growth inhibitory activity, and delta 12-PGJ2 is an ultimate metabolite exerting growth inhibition. This action appears to be independent of cAMP, since delta 12-PGJ2 was virtually inactive in raising intracellular cAMP levels.