Tumor cell biotransformation products of prostaglandin A1 with growth inhibitory activity.
The growth inhibitory effect and the fate of prostaglandin A1 (10(-6) M) were followed in cultures of rat B104 neuroblastoma and C6 glioma cells. More than 40% and 85% of the drug were neither recognized by a prostaglandin A1 antiserum nor extracted from the acidified medium with ethyl acetate, after 6 h and 24 h-incubation, respectively. When the supernatant of cells cultured in the presence of prostaglandin A1 during 24 hours was transferred to other cells and used as culture medium, the same growth inhibitory effect as with prostaglandin A1 was observed even when no prostaglandin A1 was added. After extensive purification and reverse phase HPLC of supernatant, four peaks more polar than prostaglandin A1 were shown; two of them were still active as growth inhibitors. This biotransformation was not observed with normal cells like L 929 or chick embryo fibroblasts, for which prostaglandin A1 had no inhibitory effect. The identification of these metabolites will allow the study of the structure-activity relationship.
D000818:Animals; D001711:Biotransformation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D002845:Chromatography; D003470:Culture Media; D005910:Glioma / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D011454:Prostaglandins A / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats
D003470:Culture Media; D011454:Prostaglandins A; C100573:prostaglandin A1