Document Detail

Quinolone compounds enhance {delta}-aminolevulinic acid-induced accumulation of protoporphyrin IX and photosensitivity of tumour cells.
MedLine Citation:
PMID:  20961864     Owner:  NLM     Status:  In-Data-Review    
Exogenous δ-aminolevulinic acid (ALA)-induced photodynamic therapy (PDT) has been used in the treatment of cancer. To obtain a high efficacy of ALA-PDT, we have screened various chemicals affecting ALA-induced accumulation of protoporphyrin in cancerous cells. When HeLa cells were treated with quinolone chemicals including enoxacin, ciprofloxacin or norfloxacin, the ALA-induced photodamage accompanied by the accumulation of protoporphyrin was stronger than that with ALA alone. Thus, quinolone compounds such as enoxacin, ciprofloxacin and norfloxacin enhanced ALA-induced photodamage. The increased ALA-induced photodamage in enoxacin-treated HeLa cells was decreased by haemin or ferric-nitrilotriacetate (Fe-NTA), suggesting that an increase in iron supply cancels the accumulation of protoporphyrin. On the other hand, the treatment of the cells with ALA plus an inhibitor of haem oxygenase, Sn-protoporphyrin, led to an increase in the photodamage and the accumulation of protoporphyrin compared with those upon treatment with ALA alone, indicating that the cessation of recycling of iron from haem augments the accumulation. The use of quinolones plus Sn-protoporphyrin strongly enhances ALA-induced photodamage. To examine the mechanisms involved in the increased accumulation of protoporphyrin, we incubated ferric chloride with an equivalent amount of quinolones. Iron-quinolone complexes with visible colours with a maximum at 450 nm were formed. The levels of iron-metabolizing proteins in enoxacin- or ciprofloxacin-treated cells changed, indicating that quinolones decrease iron utilization for haem biosynthesis. Hence, we now propose that the use of quinolones in combination with ALA may be an extremely effective approach for the treatment modalities for PDT of various tumour tissues in clinical practice.
Yoshiko Ohgari; Yoshinobu Miyata; Tuan Thanh Chau; Sakihito Kitajima; Yasushi Adachi; Shigeru Taketani
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Publication Detail:
Type:  Journal Article     Date:  2010-10-19
Journal Detail:
Title:  Journal of biochemistry     Volume:  149     ISSN:  1756-2651     ISO Abbreviation:  J. Biochem.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376600     Medline TA:  J Biochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  153-60     Citation Subset:  IM    
Department of Biotechnology Kyoto Institute of Technology, Kyoto 606-8585; 1st Department of Pathology, Kansai Medical University, Moriguchi, Osaka 570-8506; and Department of Biotechnology, Kyoto Institute of Technology, Kyoto 606-8585, Japan.
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