We have demonstrated, using confocal
laser scanning microscopy, that
pyridoxal treatment of B16C3 murine
melanoma cells inhibits
triamcinolone acetonide induced translocation of the
glucocorticoid receptor to the nucleus of intact cells. In addition to inhibiting
glucocorticoid receptor nuclear translocation,
pyridoxal kills B16C3 murine
melanoma cells and WM983A human
melanoma cells in culture.
Cortexolone, a
glucocorticoid antagonist, also kills cells in culture. This mechanism, however, appears to initiate in the
glucocorticoid receptor signal transducing cascade at a point prior to the impact of
pyridoxal treatment alone. The
glucocorticoid antagonist
RU486 has no detrimental effect on
melanoma cell viability, however, in combination with
pyridoxal,
RU486 extends cell viability. Since
pyridoxal kills
melanoma cells in culture, a pilot study was carried out examining the efficacy of topical application of a
pyridoxal cream to inhibit the growth and/or cause regression of (B16C3) xenograft
melanoma tumors in an immunocompetent (Hairless Rhino-J3) and an immunocompromised (Crl: nu/nu (CD1)BR) murine animal model. The results of the study with immunocompetent animals are encouraging. While
tumors are brought under control by
pyridoxal treatment, further work is needed to determine the most efficacious treatment regimen and to establish formal concentrations for
pyridoxal in topical
ointments. Trials using immunocompromised animals indicated that although some qualitative differences may be detected between the control and experimental animals,
tumor growth in these animals is so aggressive that multiple applications or higher concentrations of
pyridoxal may be needed to obtain useful data.