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M. Gehrmann, K. Pfister, P. Hutzler, R. Gastpar, B. Margulis, G. Multhoff
Effects of Antineoplastic Agents on Cytoplasmic and Membrane-Bound Heat Shock Protein 70 (Hsp70) Levels
Here we report on the study of the effects of different antineoplastic agents, including cytarabine, 4-hydroperoxyifosfamide, the activated form of ifosfamide, vincristine, and paclitaxel, with regard to their capacity to modulate the amount of cytoplasmic and membranebound heat shock protein 70 (Hsp70). Hsp70 levels were measured in the myelogenous leukemic cell line K562, in the human colon carcinoma cell line CX2, and in peripheral blood lymphocytes (PBL) under physiological conditions (37C), and following nonlethal heat shock at 41.8C. A concentration of 1 M and an incubation period of 2 h were determined as nonlethal, since none of the different antineoplastic agents induced necrosis or apoptosis in untreated or heatshocked cells under these conditions. Our results show that tubulininteracting agents, including vincristine and paclitaxel, but not DNAinteracting agents, including cytarabine and ifosfamide, selectively increase the amount of cytoplasmic Hsp70 in tumor and normal cells, as measured by semiquantitative Western blot analysis. Mechanistically, a vincristine and paclitaxelinduced tubulin assembly, as demonstrated by immunofluorescence microscopy, might be responsible for the elevated cytoplasmic Hsp70 levels. Interestingly, an increased membrane expression of Hsp70 following treatment with vincristine or paclitaxel was selectively observed on tumor cells, but not on normal cells.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 383, 11/2002
Pages: 1715 - 1725