| Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma. | |
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MedLine Citation:
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PMID: 8364920 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A bovine serum albumin-conjugated doxorubicin via the glutaraldehyde bridge (BSA-DXR conjugate) showed potent dose-dependent inhibition of cell growth against daunorubicin-resistant AH66 (AH66DR) cells as well as parental AH66 (AH66P) cells in vitro as compared to treatment with DXR or BSA-glutaraldehyde conjugate without DXR (BSA-GA). In the culture of AH66DR with BSA-DXR conjugate, drug accumulation in the AH66DR cells increased as a function of time up to 24 h reaching approximately the same drug level as AH66P cells treated with DXR. The intracellular accumulation of the BSA-DXR conjugate was inhibited by the addition of ammonium chloride, while that of DXR alone was not inhibited. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate or pharmacologically active DXR adduct remained in the cells at a relatively high concentration over a 36-h time period. The life-prolonging effect of the conjugate was assessed using rats inoculated i.p. with AH66P or AH66DR. The rats were treated with the BSA-DXR conjugate, DXR, a mixture of DXR with BSA, or BSA-GA by either the i.p. or i.v. route. Treatment with DXR had no significant surviving effect as compared to that with saline in AH66P-bearing rats. By contrast, BSA-DXR conjugate showed a significant life-prolonging effect as compared with DXR alone in the same degree both in AH66P- and AH66DR-bearing rats. BSA-GA did not show any toxicity in vivo as well as in vitro. These results indicate that the BSA-DXR conjugate allows DXR to escape from the multidrug resistance mechanism. |
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Authors:
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K Ohkawa; T Hatano; K Yamada; K Joh; K Takada; Y Tsukada; M Matsuda |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer research Volume: 53 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 1993 Sep |
Date Detail:
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Created Date: 1993-10-01 Completed Date: 1993-10-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 4238-42 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Doxorubicin / metabolism, pharmacology* Drug Resistance* Liver Neoplasms, Experimental / drug therapy*, metabolism, pathology Male Rats Serum Albumin, Bovine / metabolism, pharmacology* Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Serum Albumin, Bovine; 0/doxorubicin-BSA conjugate; 23214-92-8/Doxorubicin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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