ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P87. Solid-State NMR Study of Anticancer Cisplatin Interaction with
Phospholipid Bilayers
M. Jensen, W. Nerdal
Chemistry Department, University of Bergen, Allegaten 41, N-5007, Bergen, Norway
e-mail: magnus.jensen@kj.uib.no
Cisplatin has been used for many years in cancer chemotherapy of testicular cancer with a cure rate better than
90%[1]. Chemotherapy with use of cisplatin in treatment of other tumor types such as cervical cancers has also
been done for many years [2-4]. It is well established that cisplatin forms platinum-DNA adducts that initiate
tumor cell death [5-8]. Despite the widespread use of cisplatin in chemotherapy and its high cure rate of
testicular tumors, drawbacks are side effects such as neurotoxicity and cellular cisplatin resistance.
It is likely that the molecular mechanisms that take cisplatin across the cellular membrane are vital in the
development of cisplatin resistance with reduced intracellular accumulation. Unfortunately, these biochemical
mechanisms are not fully understood.
It is therefore important to find the molecular mechanisms of how cisplatin gets across the cellular membrane
and enters the cytosol, as well as establishing to what extent cisplatin interacts with the phospholipid bialyer. A
consequence of cisplatin binding to phospholipids of the cellular membrane is that this can change the fluidity of
the membrane and alter its function.
Results of cisplatin interaction with phospholipid bilayers studied by different NMR techniques using 1H, 13C,
31P and 15N , both magic angle spinning (MAS) and static spectra, will be presented.
References:
[1] Bosl, G. J., Bajorin, D. F. and Sheinfeld, J. Cancer of the Testis (eds, DeVita, V. T. J., Hellman, S. and
Rosenberg, S. A.) (Lippincott, Williams and Wilkins, Philadelphia, 2001).
[2] Morris, M., Eifel, P. J., Lu, J., Grigsby, P. W., Levenback, C., Stevens, R. E., Rotman, M., Gershenson, D.
M. and Mutch, D. G., N. Engl. J. Med. 340, 1137, (1999)
[3] Rose, P. G., Bundy, B. N., Watkins, E. B., Thigpen, J. T., Deppe, G., Maimann, M. A., Clarke-Pearson, D. L.
and Insalaco, S., N. Engl. J. Med. 340, 1144, (1999)
[4] Keys, H. M., Bundy, B. N., Stehman, F. B., Muderspach, L. I., Chafe, W. E., Suggs, C. L., Walker, J. L. and
Gersell, D., N. Engl. J. Med. 340, 1154, (1999)
[5] Jamieson, E. R. and Lippard, S. J., Chem. Rev. 99, 2467, (1999)
[6] Kartalou, M. and Essigman, J. M., Mut. Res. 478, 23, (2001)
[7] Brabec, V. and Kasparkova, J., Drug Resist. Updates 5, 147, (2002)
[8] Wang, D. and Lippard, S. J., Nat. Rev. 4, 307, (2005)
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