title: The effect of pentamidine on melanoma ex vivo.
abstract: Pentamidine is a small molecule inhibitor of the Ca(+)-binding protein S100B and disrupts the S100B-p53 protein-protein interaction; this is thought to restore wild-type p53 tumour suppressor function in melanoma. Additional anticancer effects may be the result of inhibition of regenerating liver family phosphatases. In this study, we have used a standardized ATP-tumour chemosensitivity assay to investigate the effect of pentamidine on cells derived from 18 skin melanoma samples and one uveal melanoma sample. The cells were tested at six concentrations from which the IC(50) and IC(90) were calculated. To allow comparison between samples, an index(sum) was calculated based on the percentage of tumour growth inhibition at each concentration. Of the skin melanoma samples tested, 78% exhibited an index(sum) less than 300 indicating strong inhibition. The median index(sum) of 237 also indicates considerable activity against these samples. The median IC(90) (30.2 micromol/l) may be clinically achievable in a proportion of patients. The uveal melanoma sample exhibited an index(sum) of 333 indicating moderate inhibition, and 86% inhibition at test drug concentration (37.96 micromol/l). These results show that pentamidine has activity against melanoma, and support the prospect of its development for therapeutic use.
authors: Translational Oncology Research Centre, Pathology Centre, Queen Alexandra Hospital, Portsmouth, UK.
authors: Jason
authors: J
authors: Smith
authors: Benjamin J
authors: BJ
authors: Stewart
authors: Sharon
authors: S
authors: Glaysher
authors: Katharine
authors: K
authors: Peregrin
authors: Louise A
authors: LA
authors: Knight
authors: David J
authors: DJ
authors: Weber
authors: Ian A
authors: IA
authors: Cree
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010419:Pentamidine / Q000494:pharmacology*; D011379:Prognosis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D010419:Pentamidine; D000255:Adenosine Triphosphate