Efficacy of pyridoxal treatment in controlling the growth of melanomas in cell culture and an animal pilot study.
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.
Maksymowych
A B
AB
Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Robertson
N M
NM
Litwack
G
G
D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D003350:Cortodoxone / Q000494:pharmacology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless; D008819:Mice, Nude; D015735:Mifepristone / Q000494:pharmacology; D010865:Pilot Projects; D011730:Pyridoxal / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015735:Mifepristone; D011730:Pyridoxal; D002784:Cholesterol; D003350:Cortodoxone