The inhibition of ferrochelatase enhances 5-aminolevulinic acid-based photodynamic action for prostate cancer

Hideo Fukuhara, Keiji Inoue, Atsushi Kurabayashi, Mutsuo Furihata, Hirofumi Fujita, Kozo Utsumi, Junzo Sasaki, Taro Shuin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: The aim of this study was to clarify the mechanism of accumulation of 5-aminolevulinic acid (ALA)-dependent protoporphyrin IX (PpIX), ALA-photodynamic therapy (PDT)-induced cell death and enhanced efficiency by a ferrochelatase inhibitor in prostate cancer PC-3 cells. Methods: The accumulation of ALA-induced PpIX in PC-3 cells was observed by fluorescence microscopy and measured by flow cytometry analysis. The efficiency of ALA-PDT was analyzed by flow cytometry and assessed by cell death, caspase-3 activity and mitochondrial membrane potential. The ALA-PDT-promoting effects of ferrochelatase inhibitors, such as deferoxamine and NOC-18, were also analyzed. We confirmed the results obtained in vivo with an animal model using nude mice. Results: ALA-induced PpIX accumulation increased in time- and ALA concentration-dependent manners. ALA-PDT decreased the levels of mitochondrial membrane potential, and induced cell death occurred by both apoptosis and necrosis. Inhibition of ferrochelatase by deferoxamine and NOC-18 led to increase of PpIX accumulation and enhanced effect of ALA-PDT in PC-3 cells. In vivo, the degeneration of tumor tissue by ALA-PDT was observed within a broader range and led to apoptosis and necrosis. Conclusion: This study demonstrated ALA-PDT induced PC-3 cell death by the mechanisms of both necrosis and apoptosis through a caspase-independent mitochondrial pathway. Inhibition of ferrochelatase enhanced these effects, suggesting that ferrochelatase played an important role in ALA-PDT. ALA-PDT could be a new modality for focal therapy of prostate cancer.

Original languageEnglish
Pages (from-to)399-409
Number of pages11
JournalPhotodiagnosis and Photodynamic Therapy
Volume10
Issue number4
DOIs
Publication statusPublished - Dec 2013

Fingerprint

Ferrochelatase
Aminolevulinic Acid
Prostatic Neoplasms
Photochemotherapy
Cell Death
Deferoxamine
Necrosis
Mitochondrial Membrane Potential
Apoptosis
Flow Cytometry
Caspases
Fluorescence Microscopy

Keywords

  • 5-Aminolevulinic acid
  • Ferrochelatase
  • Photodynamic therapy
  • Prostate cancer
  • Protoporphyrin IX

ASJC Scopus subject areas

  • Biophysics
  • Oncology
  • Dermatology
  • Pharmacology (medical)

Cite this

The inhibition of ferrochelatase enhances 5-aminolevulinic acid-based photodynamic action for prostate cancer. / Fukuhara, Hideo; Inoue, Keiji; Kurabayashi, Atsushi; Furihata, Mutsuo; Fujita, Hirofumi; Utsumi, Kozo; Sasaki, Junzo; Shuin, Taro.

In: Photodiagnosis and Photodynamic Therapy, Vol. 10, No. 4, 12.2013, p. 399-409.

Research output: Contribution to journalArticle

Fukuhara, Hideo ; Inoue, Keiji ; Kurabayashi, Atsushi ; Furihata, Mutsuo ; Fujita, Hirofumi ; Utsumi, Kozo ; Sasaki, Junzo ; Shuin, Taro. / The inhibition of ferrochelatase enhances 5-aminolevulinic acid-based photodynamic action for prostate cancer. In: Photodiagnosis and Photodynamic Therapy. 2013 ; Vol. 10, No. 4. pp. 399-409.
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AU - Utsumi, Kozo

AU - Sasaki, Junzo

AU - Shuin, Taro

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