Interactions between Antitumor Alkylphosphocholines and Membrane Sphingolipids in Langmuir Monolayers

A. Wnętrzaka, K. Łątkaa and P. Dynarowicz-Łątkab aInstitute of Physics, Jagiellonian University, W.S. Reymonta 4, 30-059 Kraków, Poland bFaculty of Chemistry, Jagiellonian University, R. Ingardena 3, 30-060 Kraków, Poland

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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 GM1 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 Gexc 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.

DOI: 10.12693/APhysPolA.125.886 PACS numbers: 68.18.-g