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The role of nitric oxide in delta-aminolevulinic acid (ALA)-induced photosensitivity of cancerous cells.

Abstract：

:Application of delta-aminolevulinic acid (ALA) results in the endogenous accumulation of protoporphyrin IX and is a useful approach in the photodynamic therapy (PDT) of cancers. To investigate the role of nitric oxide (NO) in the specific accumulation of protoporphyrin and ALA-induced PDT of cancerous cells, we transfected inducible-nitric oxide synthase (NOS2) cDNA into human embryonic kidney (HEK) 293T cells and examined the ALA-induced photo-damage as well as the accumulation of porphyrin in the cells. When the NOS2-expressing HEK293T cells were treated with ALA and then exposed to visible light, they became more sensitive to the light with accumulating porphyrins, as compared with the ALA-treated control cells. An increase in the generation of NO in transfected cells led to the accumulation of protoporphyrin with a concomitant decrease of ferrochelatase, the final step enzyme of heme biosynthesis. When mouse macrophage-like RAW264.7 cells were cultured with lipopolysaccharide and interferon-gamma, the expression of NOS2 was induced. The addition of ALA to these cells led to the accumulation of protoporphyrin and cell death upon exposure to light. The treatment of cells with an NOS inhibitor, NG-monomethyl-L-arginine acetate, resulted in the inhibition of protoporphyrin accumulation and cell death. The levels of mitochondrial ferrochelatase and rotenone-sensitive NADH dehydrogenase in the NOS2-induced cells decreased. These results indicated that the generation of NO augments the ALA-induced accumulation of protoporphyrin IX and subsequent photo-damage in cancerous cells by decreasing the levels of mitochondrial iron-containing enzymes. Based on the fact that the production of NO in cancerous cells is elevated, NO in the cells is responsible for susceptibility with ALA-induced PDT.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Yamamoto F,Ohgari Y,Yamaki N,Kitajima S,Shimokawa O,Matsui H,Taketani S

doi

10.1016/j.bbrc.2006.12.007

subject

Has Abstract

pub_date

2007-02-16 00:00:00

pages

541-6

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)02655-6

journal_volume

353

pub_type

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The role of nitric oxide in delta-aminolevulinic acid (ALA)-induced photosensitivity of cancerous cells.