Mechanism of cell death by 5-aminolevulinic acid-based photodynamic action and its enhancement by ferrochelatase inhibitors in human histiocytic lymphoma cell line U937

Takashi Amo, Noriaki Kawanishi, Masataka Uchida, Hirofumi Fujita, Eri Oyanagi, Toshihiko Utsumi, Tetsuya Ogino, Keiji Inoue, Taro Shuin, Kozo Utsumi, Junzo Sasaki

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) for tumors is based on the tumor-selective accumulation of a photosensitizer, protoporphyrin IX (PpIX), followed by irradiation with visible light. However, the molecular mechanism of cell death caused by PDT has not been fully elucidated. The 5-aminolevulinic acid (ALA)-based photodynamic action (PDA) was dependent on the accumulation of PpIX, the level of which decreased rapidly by eliminating ALA from the incubation medium in human histiocytic lymphoma U937 cells. PDA induced apoptosis characterized by lipid peroxidation, increase in Bak and Bax/Bcl-xL, decrease in Bid, membrane depolarization, cytochrome c release, caspase-3 activation, phosphatidylserine (PS) externalization. PDT-induced cell death seemed to occur predominantly via apoptosis through distribution of PpIX in mitochondria. These cell death events were enhanced by ferrochelatase inhibitors. These results indicated that ALA-based-PDA induced apoptotic cell death through a mitochondrial pathway and that ferrochelatase inhibitors might enhanced the effect of PDT for tumors even at low concentrations of ALA.

Original languageEnglish
Pages (from-to)503-515
Number of pages13
JournalCell biochemistry and function
Volume27
Issue number8
DOIs
Publication statusPublished - Dec 2009

Keywords

  • 5-aminolevulinic acid
  • Apoptosis
  • Ferrochelatase
  • Photodynamic therapy
  • Protoporphyrin IX
  • U937 cell

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

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