Roles of porphyrin and iron metabolisms in the δ-Aminolevulinic acid (ALA)-induced accumulation of protoporphyrin and photodamage of tumor cells

Yoshiko Ohgari, Yoshinobu Miyata, Taeko Miyagi, Saki Gotoh, Takano Ohta, Takao Kataoka, Kazumichi Furuyama, Shigeru Taketani

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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. When the expression of porphyrin-biosynthetic enzymes was increased, the δ-Aminolevulinic acid (ALA)-induced accumulation of protoporphyrin (PPIX) as well as photodamage was increased. Iron from heme by the HO reaction was reused for the heme production, and the decrease of the HO-1/-2 expression led to enhancement of the ALA-induced accumulation of PPIX and photodamage. The decrease of mitochondrial utilization of iron by the knockdown of mitoferrin-2 and frataxin also enhanced the ALA effect.

Original languageEnglish
Pages (from-to)1138-1145
Number of pages8
JournalPhotochemistry and Photobiology
Volume87
Issue number5
DOIs
Publication statusPublished - 2011 Sep

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry

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