title: Lipopeptide biosurfactant pseudofactin II induced apoptosis of melanoma A 375 cells by specific interaction with the plasma membrane.
abstract: In the case of melanoma, advances in therapies are slow, which raises the need to evaluate new therapeutic strategies and natural products with potential cancer cell inhibiting effect. Pseudofactin II (PFII), a novel cyclic lipopeptide biosurfactant has been isolated from the Arctic strain of Pseudomonas fluorescens BD5. The aim of this study was to investigate the effect of PFII on A375 melanoma cells compared with the effect of PFII on Normal Human Dermis Fibroblast (NHDF) cells and elucidate the underlying mechanism of PFII cytotoxic activity. Melanoma A375 cells and NHDF cells were exposed to PFII or staurosporine and apoptotic death was assessed by monitoring caspase 3-like activity and DNA fragmentation. From time-dependent monitoring of lactate dehydrogenase (LDH) release, Ca(2+) influx, and a correlation between Critical Micelle Concentration (CMC) we concluded that cell death is the consequence of plasma membrane permeabilisation by micelles. This finding suggests that pro-apoptotic mechanism of PFII is different from previously described cyclic lipopeptides. The mechanism of PFII specificity towards malignant cells remains to be discovered. The results of this study show that PFII could be a new promising anti-melanoma agent.
authors.affiliation: Department of Biotransformation, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Janek
authors.forename: Anna
authors.initials: A
authors.lastname: Krasowska
authors.forename: Agata
authors.initials: A
authors.lastname: Radwańska
authors.forename: Marcin
authors.initials: M
authors.lastname: Łukaszewicz
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003470:Culture Media; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D008823:Micelles; D010316:Particle Size; D010718:Phosphatidylserines / Q000378:metabolism; D013194:Staining and Labeling; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D000199:Actins; D017304:Annexin A5; D003470:Culture Media; D055666:Lipopeptides; D008823:Micelles; D010718:Phosphatidylserines; D013501:Surface-Active Agents; D053148:Caspase 3; D002118:Calcium