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, Ca2+ 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.
Highlights
Melanoma is the most aggressive form of skin cancer with a median survival time of 8–9 months and a 3-year survival rate of 10%–15%
The mode of action of Pseudofactin II (PFII) is different from pro-apoptotic activity of the previously described cyclic lipopeptide (CLP) [15] which did not affected membrane integrity
Impairment of membrane integrity may lead to the observed Ca2+ influx, which triggers further signaling cascades, like measured caspase-3 activation, that lead to apoptosis
Summary
Melanoma is the most aggressive form of skin cancer with a median survival time of 8–9 months and a 3-year survival rate of 10%–15%. E.g., lipopeptide and glycolipid have been found to possess antibacterial, antifungal, anti-viral, hemolytic and ionophoric properties [10,11,12]. Some of these molecules have been shown to induce apoptosis in tumor cells. A lipopeptide produced by Bacillus subtilis has anti-tumor activity on LoVo cells [13] and a cyclic lipopeptide from Bacillus natto T-2 induces apoptosis in human leukemia K562 cells [14] by an increase in [Ca2+] and Extracellular Signal-regulated Kinases (ERK) phosphorylation [15]. Glycolipids from Candida antarctica and their analogs have been implicated in growth arrest, apoptosis, and differentiation of mouse malignant melanoma and human HL60 cells [16,17]
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