Document Detail


Comparison of pharmacokinetics, intracellular localizations and sonodynamic efficacy of endogenous and exogenous protoporphyrin IX in sarcoma 180 cells.
MedLine Citation:
PMID:  20580049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The aim of the present study was to investigate the differences in pharmacokinetics, sub-cellular localizations and sonodynamic efficacy between endogenous and exogenous protoporphyrin IX (endo-PpIX and exo-PpIX) in sarcoma 180 (S180) cells. MATERIALS AND METHODS: The 5-aminolevulinic acid (ALA)-derived endo-PpIX and exo-PpIX pharmacokinetic profiles were determined by the fluorescence intensity of cell extracts with a spectrophotometer based on a standard curve. The changes in their sub-cellular localization patterns over a prolonged incubation time were evaluated by laser scanning confocal microscopy. The cytotoxic effects of 5-ALA-mediated sonodynamic therapy (ALA-SDT) and exogenous PpIX-mediated sonodynamic therapy (PpIX-SDT) were also evaluated by the MTT assay. RESULTS: The exo-PpIX showed dose-dependent pharmacokinetics in which a plateau of intra- and extracellular content was observed 45min after administration. However, the amount of ALA-derived endogenous intracellular PpIX, as well as extracellular PpIX in the same samples, showed linear accumulation with incubation time, which was independent of ALA concentration. Fluorescent imaging revealed that the exo-PpIX mainly accumulated at the plasma membrane in the early stage, whereas the ALA-derived PpIX initially localized in the mitochondria. Cells displayed sonodynamic damage by the synthesized endo-PpIX after addition of 1mM ALA for 12h, but the cytotoxicity induced by the equivalent amount of exo-PpIX was much more significant with increasing ultrasound intensities. CONCLUSIONS: Our findings suggest that endo- and exo-PpIX in S180 cells differ not only in pharmacokinetics but also in sub-cellular localizations, which may affect their sonodynamic efficacy and mechanisms of inducing cell death.
Authors:
Xiaobing Wang; Pan Wang; Wanyan Tong; Quanhong Liu
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-26
Journal Detail:
Title:  Ultrasonics     Volume:  50     ISSN:  1874-9968     ISO Abbreviation:  Ultrasonics     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-29     Completed Date:  2010-09-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050452     Medline TA:  Ultrasonics     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  803-10     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010. Published by Elsevier B.V.
Affiliation:
Key Laboratory of Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Shaanxi, Xi'an, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Survival
Equipment Design
Microscopy, Confocal
Protoporphyrins / pharmacokinetics*
Sarcoma 180 / metabolism,  therapy*
Sonication
Spectrometry, Fluorescence
Tumor Cells, Cultured
Ultrasonic Therapy / instrumentation,  methods*
Chemical
Reg. No./Substance:
0/Protoporphyrins; 553-12-8/protoporphyrin IX

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