Abstract
Selegiline (R-deprenyl), a monoamine oxidase-B (MAO-B) inhibitor, has complex pharmacological effect that contributes to treatment of neurodegenerative diseases such as Parkinson’s and presumably Alzheimer’s disease and might work as an inhibitor of tumor growth. In respect of tumorigenesis and metastasis formation, the controlled modifications of adhesion and migration have high therapeutic significance. In the present study, our purpose was to investigate cell physiological responses (adhesion, chemotaxis and proliferation) induced by selegiline, its metabolites and synthetic derivatives and to find some correlations between the molecular structure and the reported antitumor behavior of the derivatives. Our results demonstrated that both R- and S-deprenyls have the potency to elicit increased adhesion and a chemorepellent activity in monocyte model (Mono Mac 6 cell line derived from monoblastic leukemia); however, only the R-enantiomer proved to be cytotoxic. Among the metabolites R-amphetamine has retained the adhesion inducer and the chemorepellent effect of the parent drug on the most significant level. In contrast, a reversed chemotactic effect and an improved cytotoxic character were detected in the presence of fluoro group (p-fluoro-S-deprenyl). In summary, the adhesion inducer activity, chemorepellent and advantageous cytotoxic effects of selegiline and some derivatives indicate that these drug molecules might have inhibitory effects in metastasis formation in primary tumors.
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Acknowledgments
Authors express their gratitude to Professor Gyorgy Csaba for his suggestions and critical reading of the manuscript and to Ms Maria Knippel, Andrea Orban, and Andrea Kovács for their expert technical assistance. This study was supported by the Neurochemical Research Group of Hungarian Academy of Sciences, Hungarian Academy of Sciences Foundation OTKA 63415 and ETT 141/2003 Grants.
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None of the authors of the above manuscript has declared any conflict of interest.
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E. Lajkó and L. Polgár contributed equally to this work.
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Lajkó, E., Polgár, L., Láng, O. et al. Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes. J Neural Transm 119, 545–556 (2012). https://doi.org/10.1007/s00702-011-0735-1
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DOI: https://doi.org/10.1007/s00702-011-0735-1