Azelaic acid was sensitizing effect in the chemotherapeutic treatment of several melanoma cell lines.
Chemotherapy for melanoma results in low response and must be reinforced with sensitizer compounds. We believed that azelaic acid (AZA) could modulate melanomas' resistance to antineoplastics. Therefore we tried to compare in vitro treatment with antineoplastics alone versus AZA treatment followed by antineoplastics. We carried out MTT assays to evaluate the cytotoxicity of melphalan, lomustine (CCNU), fotemustine, and 4-Hydroxyanisole (4-HA) on three melanoma lines (B16F10, SK-MEL-28, and SK-MEL-1), and the modulating effect of pretreatment with AZA (1 mM). AZA showed a dose-dependent antineoplastic activity on the three lines. Melphalan was the most active drug followed by CCNU, fotemustine, and 4-HA. The most sensitive line was B16F10 and the least sensitive was SK-meL-1. Previous treatment with AZA of B16F10 reinforced the effect of melphalan (2.5 times), CCNU (10 times), and fotemustine (14 times); whereas for SK-MEL-28 and SK-MEL-1, only the cytotoxicity of CCNU and fotemustine increased. An antagonist effect was produced by 4-HA on all three lines. We concluded that AZA enhances in vitro cytotoxicity of CCNU and fotemustine.
Rodriguez-Vicente
J
J
Department of Pathology, Faculty of Medicine, Campus de Espinardo, University of Murcia, Spain.
Vicente-Ortega
V
V
Canteras-Jordana
D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008130:Lomustine / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D008855:Microscopy, Electron, Scanning; D014442:Monophenol Monooxygenase / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014617:Vacuoles / Q000187:drug effects
D000840:Anisoles; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003998:Dicarboxylic Acids; C009760:mequinol; D008130:Lomustine; D014442:Monophenol Monooxygenase; C010038:azelaic acid; D008558:Melphalan