Monitoring subcellular biotransformation of N-l-leucyldoxorubicin by micellar electrokinetic capillary chromatography coupled to laser-induced fluorescence detection

Chad P. Satori, Brandon Meyer, Edgar Arriaga

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)2389-2397
Number of pages9
JournalAnalytical and Bioanalytical Chemistry
Volume406
Issue number9-10
DOIs
StatePublished - Jan 1 2014

Fingerprint

Micellar Electrokinetic Capillary Chromatography
Biotransformation
Chromatography
Organelles
Lasers
Fluorescence
Doxorubicin
Monitoring
Prodrugs
Extracellular Space
Cytotoxicity
Sarcoma
Antineoplastic Agents
N-leucyldoxorubicin
Pharmaceutical Preparations

Keywords

  • Biotransformation
  • Doxorubicin
  • Endocytic organelles
  • Micellar electrokinetic chromatography
  • N-l-leucyldoxorubicin
  • Prodrugs

Cite this

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title = "Monitoring subcellular biotransformation of N-l-leucyldoxorubicin by micellar electrokinetic capillary chromatography coupled to laser-induced fluorescence detection",
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.]",
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author = "Satori, {Chad P.} and Brandon Meyer and Edgar Arriaga",
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AU - Satori, Chad P.

AU - Meyer, Brandon

AU - Arriaga, Edgar

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.]

AB - 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.]

KW - Biotransformation

KW - Doxorubicin

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