title: Basic cell physiological activities (cell adhesion, chemotaxis and proliferation) induced by selegiline and its derivatives in Mono Mac 6 human monocytes.
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.
authors.affiliation: Department of Genetics Cell and Immunobiology, Semmelweis University, Nagyvárad tér 4, Budapest 1089, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Lajkó
authors.forename: Lívia
authors.initials: L
authors.lastname: Polgár
authors.forename: Orsolya
authors.initials: O
authors.lastname: Láng
authors.forename: József
authors.initials: J
authors.lastname: Lengyel
authors.forename: László
authors.initials: L
authors.lastname: Kőhidai
authors.forename: Kálmán
authors.initials: K
authors.lastname: Magyar
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000633:toxicity; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D012642:Selegiline / Q000031:analogs & derivatives / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline
references.citation: Lancet. 1977 Feb 26;1(8009):439-43
references.pmid: 65560
references.citation: J Neural Transm Suppl. 1998;52:109-23
references.pmid: 9564614
references.citation: Pharm Res. 1996 Oct;13(10):1535-40
references.pmid: 8899847
references.citation: Adv Biochem Psychopharmacol. 1972;5:393-408
references.pmid: 5066229
references.citation: Acta Physiol Acad Sci Hung. 1967;32(4):377-87
references.pmid: 5595908
references.citation: Vopr Med Khim. 1997 Nov-Dec;43(6):504-14
references.pmid: 9503567
references.citation: J Neural Transm Suppl. 1994;41:167-75
references.pmid: 7931223
references.citation: Life Sci. 1991;48(6):517-21
references.pmid: 1899460
references.citation: Ann N Y Acad Sci. 2001 Jun;939:450-8
references.pmid: 11462801
references.citation: Neurobiology (Bp). 2000;8(3-4):249-55
references.pmid: 11225516
references.citation: Cell Tissue Res. 2010 Jan;339(1):83-92
references.pmid: 19921267
references.citation: Drug Metab Dispos. 1997 Jun;25(6):657-62
references.pmid: 9193866
references.citation: Mod Probl Pharmacopsychiatry. 1983;19:170-6
references.pmid: 6408405
references.citation: J Neurol Sci. 2009 Aug 15;283(1-2):182-6
references.pmid: 19332347
references.citation: Neurology. 1996 Dec;47(6 Suppl 3):S171-83
references.pmid: 8959986
references.citation: Arch Int Pharmacodyn Ther. 1965 May;155(1):154-64
references.pmid: 4378644
references.citation: J Biomol Screen. 2005 Dec;10(8):795-805
references.pmid: 16234347
references.citation: Mech Ageing Dev. 2002 Apr 30;123(8):1081-6
references.pmid: 12044957
references.citation: FEBS Lett. 1995 Jan 23;358(2):145-8
references.pmid: 7828725
references.citation: J Neuroimmunol. 2000 Sep 22;109(2):95-104
references.pmid: 10996211
references.citation: J Neural Transm (Vienna). 2001;108(1):25-33
references.pmid: 11261744
references.citation: Neurobiol Aging. 1997 Jul-Aug;18(4):431-5
references.pmid: 9330975
references.citation: Am J Ther. 1996 Oct;3(10):688-98
references.pmid: 11862224
references.citation: Toxicol Lett. 2006 Aug 20;165(2):195-202
references.pmid: 16701969
references.citation: Chem Res Toxicol. 2000 Oct;13(10):1037-45
references.pmid: 11080052
references.citation: Endocrinology. 1995 Mar;136(3):1103-10
references.pmid: 7867565
references.citation: Ann N Y Acad Sci. 1992 May 11;648:365-7
references.pmid: 1637071
references.citation: Neuroreport. 2000 Aug 3;11(11):2597-600
references.pmid: 10943729
references.citation: J Neurochem. 1994 Oct;63(4):1572-5
references.pmid: 7931312
references.citation: Br J Clin Pharmacol. 1978 Dec;6(6):542-4
references.pmid: 728327
references.citation: J Neural Transm (Vienna). 2001;108(11):1239-47
references.pmid: 11768624
references.citation: J Neural Transm. 1987;70(1-2):39-50
references.pmid: 3668521
references.citation: Acta Neurol Scand Suppl. 1989;126:93-9
references.pmid: 2515726
references.citation: Curr Med Chem. 2004 Aug;11(15):2017-31
references.pmid: 15279565
references.citation: Pol J Pharmacol Pharm. 1988 Nov-Dec;40(6):653-8
references.pmid: 3152003
references.citation: J Neurochem. 1986 May;46(5):1359-65
references.pmid: 2420928
references.citation: J Neural Transm Suppl. 1996;48:45-59
references.pmid: 8988461
references.citation: J Neural Transm. 1975;36(3-4):303-26
references.pmid: 1172524
references.citation: Anticancer Res. 1999 Nov-Dec;19(6B):5023-8
references.pmid: 10697505
references.citation: Neurotoxicology. 2004 Jan;25(1-2):233-42
references.pmid: 14697898
references.citation: J Neural Transm. 1985;64(2):113-27
references.pmid: 3935752
references.citation: J Neurochem. 1996 Oct;67(4):1532-9
references.pmid: 8858937
references.citation: Proc Natl Acad Sci U S A. 1984 Jun;81(12):3761-4
references.pmid: 6587391
references.citation: J Neural Transm (Vienna). 2005 Nov;112(11):1433-45
references.pmid: 15785858
references.citation: J Neural Transm (Vienna). 2010 Jun;117(6):695-8
references.pmid: 20454984
references.citation: Cell Adh Migr. 2009 Oct-Dec;3(4):334-6
references.pmid: 19949308