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Interactions between Antitumor Alkylphosphocholines and Membrane Sphingolipids in Langmuir Monolayers

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Alkylphosphocholines (APCs) are new generation, highly selective antineoplastic drugs, whose mechanism of action is not fully understood. It is known that in contrast to traditional chemotherapeutics, APCs do not induce cell death by apoptosis or necrosis as a result of DNA damage, but target cellular membranes and affect their biophysical properties. However, it is still unknown which membrane component attracts APC molecules selectively to cancer cells. In order to get insight into this issue, systematic investigations on the interactions between APCs and particular membrane components are highly required. Such experiments can be performed with the Langmuir monolayer technique, serving as a biomembrane model. Because of overexpression of gangliosides in tumor progression and the ability of APCs to insert into membrane rafts, two sphingolipids, i.e. sphingomyelin (SM) and ganglioside GM_1 have been examined as potential membrane targets. In this respect, their interactions with three alkylphosphocholines, differing in their hydrophobic part: hexadecylphosphocholine (HePC), octadecylphosphocholine (OcPC) and erucylphosphocholine (ErPC) have been studied and the following systems have been analysed: SM(or GM1)/HePC, SM(or GM1)/OcPC and SM(or GM1)/ErPC. It was found that all the investigated APCs show strong affinity to ganglioside in contrast to sphingomyelin. Differences in interaction of APCs with both investigated sphingolipids were studied based on experimental surface pressure (π) versus mean molecular area (A) isotherms, and analyzed qualitatively (with mean molecular area values) as well as quantitatively (with Δ G^{exc} function). The obtained results have also been analysed taking into consideration geometry of interacting molecules. Our results suggest that gangliosides may be molecular targets for APCs, attracting them to tumor cells. Although the interactions with sphingomyelin were found to be unfavourable, further studies on more complex system, containing APCs mixed with sphingomyelin and cholesterol, are required to better understand the role of lipid rafts in the selectivity of APCs.
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  • [1] C. Gajate, F. Mollinedo, Curr. Drug Metab. 3, 491 (2002), doi: 10.2174/10491
  • [2] T. Wieder, W. Reutter, C.E. Orfanos, C.C. Geilen, Prog. Lipid Res. 38, 249 (1999), doi: 10.1016/S0163-7827(99)00004-1
  • [3] C. Unger, E.A.M. Fleer, J. Kötting, W. Neumüller, H. Eibl, Prog. Exp. Tumor Res. 34, 25 (1992)
  • [4] H. Eibl, C. Unger, Cancer Treat. Rev. 17, 233 (1990), doi: 10.1016/0305-7372(90)90053-I
  • [5] V. Jendrossek, I. Müller, H. Eibl, C. Belka, Oncogene 22, 2621 (2003), doi: 10.1038/sj.onc.1206355
  • [6] C. Gajate, R.I. Fonteriz, C. Cabaner, G. Alvarez-Noves, Y. Alvarez-Rodriguez, M. Modolell, F. Mollinedo, Int. J. Cancer 85, 674 (2000), doi: 10.1002/(SICI)1097-0215(20000301)85:5<674::AID-IJC13>3.0.CO;2-Z
  • [7] S.M. Johnson, R. Robinson, Biochim. Biophys. Acta 558, 282 (1979), doi: 10.1016/0005-2736(79)90263-3
  • [8] G. Agatha, R. Hafer, F. Zintl, Cancer Lett. 173, 139 (2001), doi: 10.1016/S0304-3835(01)00674-7
  • [9] M. Sok, M. Šentjurc, M. Schara, Cancer Lett. 139, 215 (1999), doi: 10.1016/S0304-3835(99)00044-0
  • [10] M.R. Freeman, K.R. Solomon, J. Cell. Biochem. 91, 54 (2004), doi: 10.1002/jcb.10724
  • [11] S. Riedl, D. Zweytick, K. Lohner, Chem. Phys. Lipids 164, 766 (2011), doi: 10.1016/j.chemphyslip.2011.09.004
  • [12] A. Wnętrzak, K. Łątka, P. Dynarowicz-Łątka, J. Membrane Biology 246, 453 (2013), doi: 10.1007/s00232-013-9557-4
  • [13] M. Rybczyńska, M. Spitaler, N.G. Knebel, G. Boeck, H. Grunicke, J. Hofmann, Biochem. Pharm. 62, 765 (2001), doi: 10.1016/S0006-2952(01)00715-8
  • [14] A.H. Van der Luit, S.R. Vink, J.B. Klarenbeek, D. Perrissound, E. Solary, M. Verheij, W.J. Blitterswijk, Mol. Cancer Ther. 6, 2337 (2007), doi: 10.1158/1535-7163.MCT-07-0202
  • [15] T. Nieto-Miguel, C. Gajate, F. Mollinedo, J. Biol. Chem. 281, 14833 (2006), doi: 10.1074/jbc.M511251200
  • [16] A. Ausili, A. Torrecillas, F.J. Aranda, F. Mollinedo, C. Gajate, S. Corbalán-Garcia, A. de Godos, J.C. Gómez-Fernández, J. Phys. Chem. B 112, 11643 (2008), doi: 10.1021/jp802165n
  • [17] R.G. Fish, Med. Hypotheses 46, 140 (1996), doi: 10.1016/S0306-9877(96)90014-6
  • [18] G.L. Gaines Jr, Insoluble Monolayers at Liquid-Gas Interfaces, Interscience, New York 1966
  • [19] R. Maget-Dana, Biochim. Biophys. Acta 1462, 109 (1999), doi: 10.1016/S0005-2736(99)00203-5
  • [20] C. Peetla, A. Stine, L. Labhasetwar, Mol. Pharmaceut. 6, 1264 (2009), doi: 10.1021/mp9000662
  • [21] P. Dynarowicz-Łątka, K. Kita, Adv. Coll. Interface Sci. 79, 1 (1999), doi: 10.1016/S0001-8686(98)00064-5
  • [22] J.M. Smaby, H.L. Brockman, R.E. Brown, Biochemistry 33, 9135 (1994), doi: 10.1021/bi00197a016
  • [23] R. Wüstneck, N. Wüstneck, D.O. Grigoriev, U. Pison, R. Miller, Colloids Surf. B 15, 275 (1999), doi: 10.1016/S0927-7765(99)00094-6
  • [24] M. Roefzaad, T. Kluner, I. Brand, Phys. Chem. Chem. Phys. 11, 10140 (2009), doi: 10.1039/B910479H
  • [25] J.T. Davies, E.K. Rideal, Interfacial Phenomena, Academic Press, New York 1963
  • [26] S.L. Frey, E.Y. Chi, C. Arratia, J. Majewski, K. Kjaer, K.Y.C. Lee, Biophys. J. 94, 3047 (2008), doi: 10.1529/biophysj.107.119990
  • [27] J.N. Israelachvili, Intermolecular and Surface Forces, Academic Press, London 1985
  • [28] J.N. Israelachvili, S. Marcelja, R.G. Horn, Q. Rev. Biophys. 13, 121 (1980), doi: 10.1017/S0033583500001645
  • [29] P.A. Janmey, P.K.J. Kinnunen, Trends Cell Biol. 16, 538 (2006), doi: 10.1016/j.tcb.2006.08.009
  • [30] M.A. Perillo, N.J. Scarsdale, R.K. Yu, B. Maggio, Proc. Natl. Acad. Sci. USA 91, 10019 (1994), doi: 10.1073/pnas.91.21.10019
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