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Modification and uptake of a cisplatin carbonato complex by Jurkat cells
Corey R Centerwall1, Kirk A Tacka, Deborah J Kerwood
1Department of Chemistry, 111 College Place, Rm. 1-014 CST, Syracuse University, Syracuse, NY 13244-4100, USA.
Molecular Pharmacology
|April 25, 2006
Summary
Jurkat cells rapidly modify cisplatin in culture media, forming a small molecule that stays extracellular. This suggests an extracellular detoxification mechanism, impacting cisplatin
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Cisplatin is a widely used chemotherapy drug.
- Understanding cisplatin's interaction with cells is crucial for optimizing its efficacy and minimizing side effects.
Purpose of the Study:
- To investigate the interaction of Jurkat cells with cisplatin in culture.
- To elucidate the mechanism of cisplatin modification and its location (intracellular vs. extracellular).
Main Methods:
- 1H-15N heteronuclear single quantum coherence (HSQC) NMR spectroscopy.
- Inductively coupled plasma mass spectrometry (ICP-MS).
Main Results:
- Jurkat cells rapidly modify cisplatin into a monocarbonato complex (4) in culture media.
- Modified cisplatin remains extracellular (<3 kDa, HSQC NMR silent) and is not taken up by cells.
- Cells exhibit a decreasing ability to modify cisplatin over time, suggesting a limited capacity.
Conclusions:
- A novel extracellular detoxification mechanism for cisplatin by Jurkat cells is proposed.
- This mechanism involves rapid extracellular modification, preventing cellular uptake and DNA binding.
- Findings have significant implications for understanding cisplatin's mechanism of action and drug resistance.