Metabolism of Arachidonic Acid in Human Lung Cancer Cell Lines1

The metabolismof arachidonicacid(AA) was studiedintwo pulmonary hrunthioloalvi-olar-carcinomacell Unes(NCI-H322 and NOM I358) and two small cell lung carcinoma cell lines (NCI-H69 and NCI-HI28). Exogenous AA was metabolized only in the NCI-H322 and NCI-H358 cells. There was no detectable metabolism of AA in NCI-H69 or NO-HI 28 cells, either in the presence orthe absence of the calcium ionophore A23187. The majormetabolite of AA isolated from both NCI-H322 and NCI-H358 cells was prostaglandin E2 (PGF,2).Prostaglandin endoperoxide synthase activities, expressed as immnnoreactivePGE2(pmol/min/ mg protein), were 10.3 ±0.28 (SD) and 4.8 ±0.48 in NCI-H358 and NCI-H322 cells, respectively. The rate of productionof PGEj by both NCI-H358 and NCI-H322 cells was linear up to 10 min. Production of PGEj in both cell Uneswas dependent upon substrate concentrationand was maximal above 17 /»MAA. Moreover, PGE2did not undergofurther metabolism by either the NCI-H358 or the NCI-H322 cells. Aspirin (0.1 mivi),a cyclooxygenase inhibitor, decreased PGEj productionby 77 and 60% in NCI-H358 and NCI-H322 cells, respectively. In the presence of exogenous AA the calcium ionophore,A23187 (20 /IM),stimulated PGEj productionin NCI-H322 cells by almost 2-fold, although it did notaffect PGE2 productionin the NCI-H358 cells. In contrast, A23187 stimulated the endogenous productionof PGE, in both NCI-11322 and NCI-H358 cells by 4- and 9-fold respectively. In addition, both the NCI-H358 and NCI-H322 cell lines were susceptible to the cytotoxic effects of the anticanceragent mitoxantronein both a time andconcentrationdependent manner. In contrast, the two cell lines lacking detectable prostaglandin synthesis activity, NCI-H69 andNCI-H128 were unaffectedbytreatment with mitoxantrone. These results illustrate that there are major differ ences in the abilities of human lung cancer cell Unesto biosynthesize and release PGK.2.It is conceivable that such differences might have exploit able diagnostic and/or therapeutic implications. points, 0.1 or 0.2 ml of the incubation medium was removed for LDH leakage determination.