Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct

Charlotte Møller, Hanne Sørup Tastesen, Bente Gammelgaard, Ian Henry Lambert, Stefan Stürup

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Abstract

The accumulation and cytotoxicity of a 10 µmol L¿¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any significant amount within 24 h incubation. The accumulation and cytotoxicity of HSA-Pt was compared to 10 µmol L¿¹ cisplatin for which a larger accumulation and cytotoxicity were observed in EATC compared to Lettré. The experiment was performed with cell medium exchange every fourth hour as HSA-Pt and cisplatin were not stable in RPMI-1640 with 10% serum. The stability was determined using size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and after 4 h new platinum peaks were observed. These findings indicate that before conducting cell experiments, the stability of the compound in the cell medium should be investigated especially when long exposure times are applied. Furthermore, HSA-Pt was found to be stable in Hanks Balanced Saline Solution (HBSS) and in Phosphate Buffered Saline (PBS) at pH 5.3, 6.1 and 7.4. Thus, the shift in pH when HSA-cisplatin passes from blood (pH 7.4) to tumor tissue (pH 5-6) is not capable of releasing cisplatin from HSA.
Original languageEnglish
JournalMetallomics
Volume2
Issue number12
Pages (from-to)811-818
Number of pages8
ISSN1756-5901
DOIs
Publication statusPublished - 1 Dec 2010

Keywords

  • Cell Line, Tumor
  • Cisplatin
  • Cytotoxins
  • Humans
  • Metalloproteins
  • Platinum
  • Serum Albumin

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