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Roles of Porphyrin and Iron Metabolisms in the δ‐Aminolevulinic Acid (ALA)‐induced Accumulation of Protoporphyrin and Photodamage of Tumor Cells
Author(s) -
Ohgari Yoshiko,
Miyata Yoshinobu,
Miyagi Taeko,
Gotoh Saki,
Ohta Takano,
Kataoka Takao,
Furuyama Kazumichi,
Taketani Shigeru
Publication year - 2011
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2011.00950.x
Subject(s) - protoporphyrin , protoporphyrin ix , heme , hela , porphyrin , chemistry , heme oxygenase , transfection , biochemistry , gene knockdown , microbiology and biotechnology , enzyme , photodynamic therapy , cell , biology , apoptosis , gene , organic chemistry
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 photodamage. 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 photodamage 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 photodamage. The ALA effect was decreased with HeLa cells expressing mitoferrin‐2, a mitochondrial iron transporter, whereas it was enhanced by the mitoferrin‐2 siRNA transfection. These results indicated that not only the production of porphyrin intermediates but also the reuse of iron from heme and mitochondrial iron utilization control the ALA‐induced accumulation of protoporphyrin in cancerous cells.