TY - JOUR
T1 - New extracellular resistance mechanism for cisplatin
AU - Centerwall, Corey R.
AU - Kerwood, Deborah J.
AU - Goodisman, Jerry
AU - Toms, Bonnie B.
AU - Dabrowiak, James C.
PY - 2008/5
Y1 - 2008/5
N2 - The HSQC NMR spectrum of 15N-cisplatin in cell growth media shows resonances corresponding to the monocarbonato complex, cis-[Pt(NH3)2(CO3)Cl]-, 4, and the dicarbonato complex, cis-[Pt(NH3)2(CO3)2]-2, 5, in addition to cisplatin itself, cis-[Pt(NH3)2Cl2], 1. The presence of Jurkat cells reduces the amount of detectable carbonato species by (2.8 ± 0.7) fmol per cell and has little effect on species 1. Jurkat cells made resistant to cisplatin reduce the amount of detectable carbonato species by (7.9 ± 5.6) fmol per cell and also reduce the amount of 1 by (3.4 ± 0.9) fmol per cell. The amount of detectable carbonato species is also reduced by addition of the drug to medium that has previously been in contact with normal Jurkat cells (cells removed); the reduction is greater when drug is added to medium previously in contact with resistant Jurkat cells (cells removed). This shows that the platinum species are modified by a cell-produced substance that is released to the medium. Since the modified species have been shown not to enter or bind to cells, and since resistant cells modify more than non-resistant cells, the modification constitutes a new extracellular mechanism for cisplatin resistance which merits further attention.
AB - The HSQC NMR spectrum of 15N-cisplatin in cell growth media shows resonances corresponding to the monocarbonato complex, cis-[Pt(NH3)2(CO3)Cl]-, 4, and the dicarbonato complex, cis-[Pt(NH3)2(CO3)2]-2, 5, in addition to cisplatin itself, cis-[Pt(NH3)2Cl2], 1. The presence of Jurkat cells reduces the amount of detectable carbonato species by (2.8 ± 0.7) fmol per cell and has little effect on species 1. Jurkat cells made resistant to cisplatin reduce the amount of detectable carbonato species by (7.9 ± 5.6) fmol per cell and also reduce the amount of 1 by (3.4 ± 0.9) fmol per cell. The amount of detectable carbonato species is also reduced by addition of the drug to medium that has previously been in contact with normal Jurkat cells (cells removed); the reduction is greater when drug is added to medium previously in contact with resistant Jurkat cells (cells removed). This shows that the platinum species are modified by a cell-produced substance that is released to the medium. Since the modified species have been shown not to enter or bind to cells, and since resistant cells modify more than non-resistant cells, the modification constitutes a new extracellular mechanism for cisplatin resistance which merits further attention.
KW - Cisplatin
KW - Extracellular
KW - HSQC NMR
KW - Resistance
UR - http://www.scopus.com/inward/record.url?scp=41949107795&partnerID=8YFLogxK
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U2 - 10.1016/j.jinorgbio.2008.01.008
DO - 10.1016/j.jinorgbio.2008.01.008
M3 - Article
C2 - 18294693
AN - SCOPUS:41949107795
SN - 0162-0134
VL - 102
SP - 1044
EP - 1049
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 5-6
ER -