The metabolism of arachidonic acid (AA) was studied in two pulmonary bronchioloalveolar-carcinoma cell lines (NCl-H322 and NCI-H358) and two small cell lung carcinoma cell lines (NCI-H69 and NCI-H128). Exogenous AA was metabolized only in the NCI-H322 and NCI-11358 cells. There was no detectable metabolism of AA in NCI-H69 or NO-H128 cells, either in the presence or the absence of the calcium ionophore A23187. The major metabolite of AA isolated from both NO-H322 and NO-H358 cells was prostaglandin E2 (PGEi). Prostaglandin endoperoxide synthase activities, expressed as immanoreaedve PGE2 (pmol/aria/ mg protein), were 10.3 ± 0.28 (SD) and 4.8 ± 0.48 in NO-H358 and NO-H322 cells, respectively. The rate of production of PGE2 by both NO-H358 and NCI-H322 cells was linear up to 10 min. Prodnction of PGE2 in both cell lines was dependent upon substrate concentration and was maximal above 17 μMAA. Moreover, PGE2 did not undergo further metabolism by either the NO-H358 or the NO-H322 cells. Aspirin (0.1 MM),a cyclooxygenase inhibitor, decreased PGE2 prodnction by 77 and 60% in NCI-H358 and NCI-H322 cells, respectively. In the presence of exogenous AA the calriam ionophore, A23187 (20 μM% stimulated PGE2 prodnction in Ncl-H322 cells by almost 2-fold, although it did not affect PGE2 prodnction in the NO-H358 cells. In contrast, A23187 stimulated the endogenous prodnction of PGE2 in both NO-H322 and NO-H358 cells by 4 and 9-fold respectively. In addition, both the NO-H358 and NO-H322 cell lines were susceptible to the cytotoxic effects of the anticancer agent mhoxantroue in both a time and concentration dependent manner. In contrast, the two cell lines lacking detectable prostaglandin synthesis activity, NCI-H69 and NO-H128 were unaffected by treatment with mitoxantrome. These results illustrate that there are major differences in the abilities of human lung cancer cell lines to biosynthesize and release PGE2. It is conceivable that such differences might have exploitable diagnostic and/or therapeutic implications.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Jul 1987|
ASJC Scopus subject areas
- Cancer Research