In vitro antitumor activity of MIC2 protein-doxorubicin conjugates |
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Authors: | Gabor F Haberl I Wirth M Richter K Theyer G Baumgartner G Wenzl E Hamilton G |
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Affiliation: | SALZBURG UNIV,SCH MED,DEPT SURG,A-5020 SALZBURG,AUSTRIA. SALZBURG UNIV,INST BIOCHEM,A-5020 SALZBURG,AUSTRIA. KH LAINZ,LUDWIG BOLTZMANN INST CLIN ONCOL,VIENNA,AUSTRIA. |
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Abstract: | The pseudoautosomal encoded MIC2 glycoprotein is a tumor-associated antigen of Ewing's sarcoma (ES) and closely related tumors of unknown function. To investigate the use of this protein as selective drug carrier recombinant MIC2 was coupled to doxorubicin by a two step glutaraldehyde method (molar ratio DOX/MIC2 of 32 and 16). The conjugates showed dose-dependent cytostatic activity against the ES cell line SK-ES1, the peripheral neuroectodermal line KAL and the prostate cancer cell line PC-3 concurrent with reduced toxicity against normal lymphoblasts. In comparison to free doxorubicin the MIC2-doxorubicin conjugates exhibited highest activity against the PC-3 cell line. Confocal microscopy showed intracellular accumulation of MIC2 conjugates. |
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