Document Detail


Selective tumor cell targeting by the disaccharide moiety of bleomycin.
MedLine Citation:
PMID:  23379863     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In a recent study, the well-documented tumor targeting properties of the antitumor agent bleomycin (BLM) were studied in cell culture using microbubbles that had been derivatized with multiple copies of BLM. It was shown that BLM selectively targeted MCF-7 human breast carcinoma cells but not the "normal" breast cell line MCF-10A. Furthermore, it was found that the BLM analogue deglycobleomycin, which lacks the disaccharide moiety of BLM, did not target either cell line, indicating that the BLM disaccharide moiety is necessary for tumor selectivity. Not resolved in the earlier study were the issues of whether the BLM disaccharide moiety alone is sufficient for tumor cell targeting and the possible cellular uptake of the disaccharide. In the present study, we conjugated BLM, deglycoBLM, and BLM disaccharide to the cyanine dye Cy5**. It was found that the BLM and BLM disaccharide conjugates, but not the deglycoBLM conjugate, bound selectively to MCF-7 cells and were internalized. The same was also true for the prostate cancer cell line DU-145 (but not for normal PZ-HPV-7 prostate cells) and for the pancreatic cancer cell line BxPC-3 (but not for normal SVR A221a pancreas cells). The targeting efficiency of the disaccharide was only slightly less than that of BLM in MCF-7 and DU-145 cells and comparable to that of BLM in BxPC-3 cells. These results establish that the BLM disaccharide is both necessary and sufficient for tumor cell targeting, a finding with obvious implications for the design of novel tumor imaging and therapeutic agents.
Authors:
Zhiqiang Yu; Ryan M Schmaltz; Trevor C Bozeman; Rakesh Paul; Michael J Rishel; Krystal S Tsosie; Sidney M Hecht
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-13
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  135     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-27     Completed Date:  2013-08-12     Revised Date:  2014-02-28    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2883-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Bleomycin / chemistry*
Disaccharides / chemistry*
Female
Humans
MCF-7 Cells
Grant Support
ID/Acronym/Agency:
CA140471/CA/NCI NIH HHS; R01 CA140471/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Disaccharides; 11056-06-7/Bleomycin
Comments/Corrections

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