Azidothymidine inhibits melanoma cell growth in vitro and in vivo.
Azidothymidine (AZT), currently used for HIV treatment, was also shown to induce cell growth inhibition and apoptosis in different human tumors. The objective of this study was to investigate the ability of AZT to inhibit the growth of human melanoma cells in vitro and in vivo. In cytotoxicity assays, treatment of cells with varying concentrations of AZT-induced inhibition of cell growth and apoptosis in three human melanoma cell lines without affecting the growth of nontumorigenic cells. AZT-dependent inhibition of proliferation was accompanied by a significant S-phase arrest of the cell cycle. Coexposure of cells to AZT during cisplatin treatment showed a synergistic effect on cytotoxicity. Moreover, AZT monotreatment of melanoma in a severe combined immunodeficiency-mouse xenotransplantation model resulted in significant tumor reduction. These results demonstrate for the first time the antimelanoma activity of AZT, suggesting its clinical utilization either as a sole agent or in combination with other chemotherapeutic agents.
Humer
Johannes
J
Department of Dermatology, Division of General Dermatology, Medical University of Vienna, Waehringer Guertel, Vienna, Austria.
Ferko
Boris
B
Waltenberger
Andrea
A
Rapberger
Ronald
R
Pehamberger
Hubert
H
Muster
Thomas
T
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011897:Random Allocation; D016196:S Phase / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D015215:Zidovudine; D002945:Cisplatin