Issue 12, 2010

Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct

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.

Graphical abstract: Stability, accumulation and cytotoxicity of an albumin-cisplatin adduct

Article information

Article type
Paper
Submitted
12 Sep 2010
Accepted
19 Oct 2010
First published
09 Nov 2010

Metallomics, 2010,2, 811-818

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