Botulinum Toxin Type-A Toxinactivity in Prostate Cancer Cell Lines

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Abstract
Aim of the study: Botulinum toxin A (BoNT/A) has been recently used in the treatment of benign prostatic hyperplasia due to its apoptotic activity on prostatic epithelium but few data exist on this issue in prostate cancer. Also no information exist on the eventual modulation exerted by the neurotoxin on Phospholipase A2 (PLA2) expression in prostate cancer. The aim of this study was to evaluate the activity of BoNT/A on cell growth and expression of PLA2 in prostate cancer lines. Materials and Methods: PC-3 and LNCaP cell lines were exposed to BoNT/A (Xeomin®), different doses and time of exposure. Presence of SV2 receptors (SV2-A and SV2-B) for the neurotoxin was also investigated. The expression of P-Ser505-cPLA2-α (phosphorylated enzyme) was performed immunofluorescence. Results: After 96 hours of BoNT/A administration a 20% reduction of cell growth in LNCaP and 25% in PC-3 were observed. SV-2 receptors were expressed in both cell lines. No cPLA2–α total expression was found in LnCaP. In PC-3 there was a high expression of cPLA2–α total which was not modified after BoNT/A treatment. In both LNCap and PC-3 the expression of P-Ser505-cPLA2-α (phosphorylated enzyme) increases significantly after treatment with [10 U/ml] of BoNT/A. Conclusions: LNCaP and PC-3 cell lines are sensitive to treatment with BoNT/A which probably enters the cells by SV2 receptors. The increase in the phosphorylated form of cPLA2-a, induced by BoNT/A may represent one mechanism by which the toxin reduces cell growth and proliferation.

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