The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.
Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells,...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4379089?pdf=render |
| _version_ | 1828197792751812608 |
|---|---|
| author | Maiko Hayashi Hideo Fukuhara Keiji Inoue Taro Shuin Yuichiro Hagiya Motowo Nakajima Tohru Tanaka Shun-ichiro Ogura |
| author_facet | Maiko Hayashi Hideo Fukuhara Keiji Inoue Taro Shuin Yuichiro Hagiya Motowo Nakajima Tohru Tanaka Shun-ichiro Ogura |
| author_sort | Maiko Hayashi |
| collection | DOAJ |
| description | Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects. |
| first_indexed | 2024-04-12T10:25:27Z |
| format | Article |
| id | doaj.art-fbbf326732fa442faea492714117a89b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T10:25:27Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fbbf326732fa442faea492714117a89b2022-12-22T03:36:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012235110.1371/journal.pone.0122351The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.Maiko HayashiHideo FukuharaKeiji InoueTaro ShuinYuichiro HagiyaMotowo NakajimaTohru TanakaShun-ichiro OguraRecently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.http://europepmc.org/articles/PMC4379089?pdf=render |
| spellingShingle | Maiko Hayashi Hideo Fukuhara Keiji Inoue Taro Shuin Yuichiro Hagiya Motowo Nakajima Tohru Tanaka Shun-ichiro Ogura The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid. PLoS ONE |
| title | The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid. |
| title_full | The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid. |
| title_fullStr | The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid. |
| title_full_unstemmed | The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid. |
| title_short | The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid. |
| title_sort | effect of iron ion on the specificity of photodynamic therapy with 5 aminolevulinic acid |
| url | http://europepmc.org/articles/PMC4379089?pdf=render |
| work_keys_str_mv | AT maikohayashi theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT hideofukuhara theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT keijiinoue theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT taroshuin theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT yuichirohagiya theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT motowonakajima theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT tohrutanaka theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT shunichiroogura theeffectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT maikohayashi effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT hideofukuhara effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT keijiinoue effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT taroshuin effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT yuichirohagiya effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT motowonakajima effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT tohrutanaka effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid AT shunichiroogura effectofironiononthespecificityofphotodynamictherapywith5aminolevulinicacid |