title: The effect of tricyclic antidepressants on cutaneous melanoma cell lines and primary cell cultures.
abstract: The tricyclic antidepressants have previously been shown to exert activity against glioma cells in vitro. Initial studies in cell lines suggested that this might extend to melanoma cells. We have therefore conducted a study in primary cell cultures from metastatic cutaneous melanoma deposits using a well established ATP-based tumour chemosensitivity assay to confirm and extend these findings. Two cell lines and eight primary cell cultures from metastatic melanoma deposits were exposed to three tricyclic drugs, amitriptyline, nortriptyline and clomipramine, at concentrations ranging from 200 to 6.25 µmol/l in the ATP-based tumour chemosensitivity assay. All three drugs showed activity, although nortriptyline was more active than clomipramine or amitriptyline in both cell lines and primary cell cultures, with an IC50 of 9, 27 and 33 µmol/l, respectively. Tricyclic agents show activity against melanoma in vitro. This could be related to the lysosomal effects based on their cationic amphiphilic properties, or effects at the mitochondrial membrane.
authors: Department of Cellular Pathology, Translational Oncology Research Centre, Queen Alexandra Hospital, Portsmouth, UK.
authors: Katharine A
authors: KA
authors: Parker
authors: Sharon
authors: S
authors: Glaysher
authors: Jeremy
authors: J
authors: Hurren
authors: Louise A
authors: LA
authors: Knight
authors: Deidre
authors: D
authors: McCormick
authors: Anne
authors: A
authors: Suovouri
authors: Verena
authors: V
authors: Amberger-Murphy
authors: Geoffrey J
authors: GJ
authors: Pilkington
authors: Ian A
authors: IA
authors: Cree
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002997:Clomipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009661:Nortriptyline / Q000494:pharmacology; D061251:Primary Cell Culture; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D009661:Nortriptyline; D002997:Clomipramine