Document Detail


Roles of porphyrin and iron metabolisms in the δ-aminolevulinic acid (ALA)-induced accumulation of protoporphyrin and photo-damage of tumor cells.
MedLine Citation:
PMID:  21668870     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
δ-Aminolevulinic acid (ALA)-induced porphyrin accumulation is widely used in the treatment of cancer, as photodynamic therapy. To clarify the mechanisms of the tumor-preferential accumulation of protoporphyrin, we examined the effect of the expression of heme-biosynthetic and -degradative enzymes on the ALA-induced accumulation of protoporphyrin as well as photo-damage. The transient expression of heme-biosynthetic enzymes in HeLa cells caused variations of the ALA-induced accumulation of protoporphyrin. When ALA-treated cells were exposed to white light, the extent of photo-damage of the cells was dependent on the accumulation of protoporphyrin. The decrease of the accumulation of protoporphyrin was observed in the cells treated with inducers of heme oxygenase (HO)-1. The ALA-dependent accumulation of protoporphyrin was decreased in HeLa cells by transfection with HO-1 and HO-2 cDNA. Conversely, knockdown of HO-1/-2 with siRNAs enhanced the ALA-induced protoporphyrin accumulation and photo-damage. The ALA effect was decreased with HeLa cells expressing mitoferrin-2, a mitochondrial iron transporter, while it was enhanced by the mitoferrin-2 siRNA transfection. These results indicated that not only the production of porphyrin intermediates but also the re-use of iron from heme and mitochondrial iron utilization control the ALA-induced accumulation of protoporphyrin in cancerous cells.
Authors:
Yoshiko Ohgari; Yoshinobu Miyata; Taeko Miyagi; Saki Gotoh; Takano Ohta; Takao Kataoka; Kazumichi Furuyama; Shigeru Taketani
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-14
Journal Detail:
Title:  Photochemistry and photobiology     Volume:  -     ISSN:  1751-1097     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376425     Medline TA:  Photochem Photobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Photochemistry and Photobiology © 2011 American Society for Photobiology.
Affiliation:
Department of Biotechnology Insect Biomedical Center, Kyoto Institute of Technology, Kyoto 606-8585, Japan Department of Molecular Biology and Applied Physiology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-9575, Japan.
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