SYNERGISTIC EFFECTS OF 13-CIS RETINOIC ACID AND ARACHIDONIC-ACID CASCADE INHIBITORS ON GROWTH OF HEAD AND NECK SQUAMOUS-CELL CARCINOMA IN-VITRO

Products of arachidonic acid metabolism can influence normal and malig nant cell growth, In vivo, inhibitors of arachidonic acid metabolism h ave been associated with inhibition of tumor growth, including head an d neck squamous cell carcinoma (HNSCC), This has not been evaluated ex tensively in vitro in an HNSCC model. Therefore we investigated the ef fects of several arachidonic acid cascade inhibitors (AACIs) (indometh acin, curcumin, phenidone, nordihydroguaiaretic acid, 5,8,11,14-eicosa tetraynoic acid, and 13-cisretinoic acid) on the growth of two HNSCC c ell lines (MDA 886Ln and 1483). We found that AACIs caused dose-depend ent growth inhibition of both cell lines. In an effort to inhibit HNSC C cell growth at lower concentrations of these drugs, we evaluated the effects of a variety of AACIs in combination with 13-cis retinoic aci d, We observed synergistic growth inhibition when the drugs were used in all combinations, with the exception of indomethacin. These results suggest that AACIs may have some utility in the direct treatment of H NSCC, and a strategy combining 13-cis retinoic acid with other AACIs m ay prove to be even more effective.