Melanoma is a highly malignant and increasingly common tumour. Since metastatic
melanoma remains incurable, new treatment approaches are needed. Previously, we reported that the synthetic
retinoid N-(4-hydroxyphenyl)retinamide (
fenretinide, HPR) induces apoptosis in
neuroblastoma cells, sharing a neuroectodermal origin with
melanoma cells. Since no data exist thus far on the effects of HPR on human
melanoma tumours, our purpose was to investigate the in vitro modulation of cell growth and apoptosis by HPR in
melanoma cells. Ten human
melanoma cell lines were exposed in vitro to increasing concentrations of HPR. Dose-dependent growth inhibition and cytotoxicity were observed. According to cytofluorimetric analysis,
propidium iodide staining and TUNEL assay, HPR-treated
melanoma cells were shown to undergo apoptosis. However, IC50 values ranged from 5 to 28 microM, while IC90 values were between 10 and 45 microM. These last concentrations are approximately 10-fold higher than those achievable in patients given oral HPR. To explore the potential of new delivery strategies, HPR was loaded at high concentrations into immunoliposomes directed to disialoganglioside GD2, a tumour-specific
antigen extensively expressed by neuroectoderma-derived tumours. Treatment of
melanoma cells for a short time (2 hr) with HPR-containing immunoliposomes followed by culture in
drug-free medium gave rise to apoptosis of target cells, whereas cells treated for 2 hr with equivalent concentrations of the free
drug survived. The efficacy of immunoliposomal HPR was strongly dependent on the density of GD2 expression in the different cell lines.