Document Detail


Potentiation of photodynamic therapy by ursodeoxycholic acid.
MedLine Citation:
PMID:  11156400     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ursodeoxycholic acid (UDCA) protects cells from the apoptotic effects of hydrophobic bile acids and some other cytotoxic agents. We observed the opposite result when assessing the effects of UDCA on the apoptotic response to mitochondrial photodamage induced by photodynamic therapy (PDT). Two photosensitizers with predominantly mitochondrial specificity were used: a porphycene we have designated CPO; and the tin etiopurpurin SnET2. UDCA potentiated the loss of mitochondrial potential, release of cytochrome c into the cytosol, activation of caspase-3, and apoptotic cell death after irradiation of photosensitized murine leukemia L1210 or hepatoma 1c1c7 cells. These effects were not observed when UDCA was added after irradiation. Glyco-UDCA and tauro-UDCA, conjugated forms of UDCA that are formed in vivo, were as effective as UDCA in promoting PDT phototoxicity. Because UDCA does not act by enhancing intracellular accumulation of the photosensitizing agents used in this study, we propose that the mode of action of UDCA involves the sensitization of mitochondrial membranes to photodamage. UDCA is used currently in gastroenterology for several indications. The drug may offer a means for promoting the efficacy of PDT with minimal adverse effects.
Authors:
D Kessel; J A Caruso; J J Reiners
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  60     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-11     Completed Date:  2001-02-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6985-8     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. dhkessel@med.wayne.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Blotting, Western
Caspase 3
Caspases / metabolism
Cell Survival / drug effects,  radiation effects
Cholagogues and Choleretics / therapeutic use
Cytochrome c Group / metabolism
Cytosol / metabolism
Dose-Response Relationship, Drug
Dose-Response Relationship, Radiation
Enzyme Activation
Intracellular Membranes / drug effects,  radiation effects
Mice
Microscopy, Fluorescence
Mitochondria / drug effects,  radiation effects
Photochemotherapy*
Tumor Cells, Cultured
Ursodeoxycholic Acid / analogs & derivatives*,  therapeutic use*
Grant Support
ID/Acronym/Agency:
CA23378/CA/NCI NIH HHS; ES09392/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Cholagogues and Choleretics; 0/Cytochrome c Group; 128-13-2/Ursodeoxycholic Acid; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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