DIFFERENTIAL-EFFECTS OF RETINOIC ACID AND N-(4-HYDROXPHENYL)RETINAMIDE ON HEAD AND NECK SQUAMOUS-CELL CARCINOMA-CELLS

Both retinoic acid (RA) and the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4HPR) have shown efficacy in head and neck cancer chemopre vention trials. To compare their activity and mechanism of action, the 1483 oral head and neck squamous cell carcinoma (HNSCC) cell line was grown in organotypic culture, an in vitro system that allows cellular stratification and simulates carcinoma in situ, and was exposed to 10 mu mol/L of either RA or 4HPR. Extensive apoptosis, as evidenced by i n situ deoxyribonucleic acid end-labeling, occurred in 4HPR-treated cu ltures after 9 days, with >80% cell loss (P<.001). In contrast, the gr owth of cultures treated with RA was inhibited by only 32%, with no ev idence of apoptosis. Because 4HPR has low systemic toxicity and is a p otent inducer of apoptosis in HNSCC cells, its role in chemoprevention of head and neck cancers, including cancers that are resistant to RA- induction therapy, warrants further investigation.