Clin Cancer Res
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Retinoids have been shown to act as cytostatic agents against a variety of tumor cell types, including squamous carcinoma cells. Recently it was reported that certain retinoids can induce apoptosis as well. Because we are investigating the potential of retinoids in chemoprevention and therapy for head and neck premalignant and malignant lesions, we compared the effects of all-trans-retinoic acid (ATRA) and N-(4-hydroxyphenyl)retinamide (4HPR) on seven human head and neck squamous cell carcinoma cell lines (17A, 17B, 22A, 22B, 38, SqCC/Y1, and 1483). ⋯ In 17B cells, a clear DNA ladder was observed as early as 2 days after treatment with 4HPR; however, neither ATRA nor 9-cis-retinoic acid was as effective. In addition, morphological changes associated with apoptotic cell death, such as chromatin condensation and nuclear segmentation, were observed by propidium iodide staining and by electron microscopic analysis after 4HPR treatment. These results demonstrate that 4HPR causes apoptosis in several head and neck squamous cell carcinoma cell lines and that it is more potent in this effect than ATRA.