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

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.

• Authors: Yoshiko Ohgari, Yoshinobu Miyata, Taeko Miyagi, Saki Gotoh, Takano Ohta, Takao Kataoka, Kazumichi Furuyama, Shigeru Taketani
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2011 Sep-Oct Vol. 87 Issue 5 Pg. 1138-45 ISSN: 1751-1097 [Electronic] United States
• PMID: 21668870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Chemical References

• Cation Transport Proteins
• Photosensitizing Agents
• Protoporphyrins
• RNA, Small Interfering
• SLC25A28 protein, human
• Heme
• Aminolevulinic Acid
• Iron
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• heme oxygenase-2

Topics

• Aminolevulinic Acid (metabolism, pharmacology)
• Cation Transport Proteins (genetics, metabolism)
• Cell Survival (drug effects, radiation effects)
• Female
• Gene Silencing (drug effects)
• HeLa Cells
• Heme (metabolism)
• Heme Oxygenase (Decyclizing) (antagonists & inhibitors, genetics, metabolism)
• Heme Oxygenase-1 (antagonists & inhibitors, genetics, metabolism)
• Humans
• Iron (metabolism)
• Light
• Mitochondria (drug effects, metabolism, radiation effects)
• Photochemotherapy
• Photosensitizing Agents (metabolism, pharmacology)
• Plasmids
• Protoporphyrins (biosynthesis)
• RNA, Small Interfering (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Transfection
• Uterine Cervical Neoplasms (drug therapy, metabolism, pathology)