Abstract
Development of prodrugs is a promising alternative to address cytotoxicity and nonspecificity of common anticancer agents. N-l-leucyldoxorubicin (LeuDox) is a prodrug that is biotransformed to the anticancer drug doxorubicin (Dox) in the extracellular space; however, its biotransformation may also occur intracellularly in endocytic organelles. Such organelle-specific biotransformation is yet to be determined. In this study, magnetically enriched endocytic organelle fractions from human uterine sarcoma cells were treated with LeuDox. Micellar electrokinetic chromatography with laser-induced fluorescence detection (MEKC-LIF) was used to determine that 10 % of LeuDox was biotransformed to Dox, accounting for 43 % of the biotransformation occurring in the post-nuclear fraction. This finding suggests that endocytic organelles also participate in the intracellular biotransformation of LeuDox to Dox. [Figure not available: see fulltext.]
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2389-2397 |
| Number of pages | 9 |
| Journal | Analytical and Bioanalytical Chemistry |
| Volume | 406 |
| Issue number | 9-10 |
| DOIs | |
| State | Published - Apr 2014 |
Bibliographical note
Funding Information:Acknowledgments C.S. was supported by NIH grant T32 GM008347. B.M. was sponsored by the University of Minnesota’s Undergraduate Research Opportunities Program. We would like to thank Joseph J. Dalluge for his assistance with mass spectrometry and George Barany for his guidance on the synthesis of LeuDox.
Keywords
- Biotransformation
- Doxorubicin
- Endocytic organelles
- Micellar electrokinetic chromatography
- N-l-leucyldoxorubicin
- Prodrugs
