Abstract
The antitumor properties of ticks salivary gland extracts or recombinant proteins have been reported recently, but little is known about the antitumor properties of the secreted components of saliva. The goal of this study was to investigate the in vitro effect of the saliva of the hard tick Amblyomma sculptum on neuroblastoma cell lines. SK-N-SK, SH-SY5Y, Be(2)-M17, IMR-32, and CHLA-20 cells were susceptible to saliva, with 80% reduction in their viability compared to untreated controls, as demonstrated by the methylene blue assay. Further investigation using CHLA-20 revealed apoptosis, with approximately 30% of annexin-V positive cells, and G0/G1-phase accumulation (>60%) after treatment with saliva. Mitochondrial membrane potential (Δψm) was slightly, but significantly (p < 0.05), reduced and the actin cytoskeleton was disarranged, as indicated by fluorescent microscopy. The viability of human fibroblast (HFF-1 cells) used as a non-tumoral control decreased by approximately 40%. However, no alterations in cell cycle progression, morphology, and Δψm were observed in these cells. The present work provides new perspectives for the characterization of the molecules present in saliva and their antitumor properties.
Highlights
Ticks are specialized hematophagous ectoparasites of significant medical and public health importance (RANDOLPH, 2009)
A. sculptum crude saliva (CS) decreased the viability of all NB cell lines
We found that the CS of A. sculptum, exhibited cytotoxic effects on different human NB cells, supporting the antitumor potential of CS, as reported by Sousa et al (2015)
Summary
Ticks are specialized hematophagous ectoparasites of significant medical and public health importance (RANDOLPH, 2009). As a source of anti-neoplasic compounds, it has been reported that tick saliva constituents can affect cancer cell proliferation (KAZIMIROVA et al, 2006), apoptosis (AKAGI et al, 2012), migration and invasion (POOLE et al, 2013), and tumor growth and angiogenesis (CARNEIRO-LOBO et al, 2009). The cytotoxicity of Amblyomma sculptum Berlese crude saliva (CS) has been demonstrated in melanoma, pancreatic adenocarcinoma (SIMONS et al, 2011), and breast cancer cells (SOUSA et al, 2018). Neuroblastoma (NB) is the most common extracranial solid pediatric tumor. These tumors, which account for 15% of pediatric cancer deaths, occur preferentially in young children with a median age at diagnosis of 18 months (KAMIHARA et al, 2017). In the last 30 years, significant progress has been achieved in the treatment for high-risk NB, the long-term survival for this group of patients remains under 50%, emphasizing the need for more effective treatments (PINTO et al, 2015)
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