title: Mechanism of cell death by 5-aminolevulinic acid-based photodynamic action and its enhancement by ferrochelatase inhibitors in human histiocytic lymphoma cell line U937.
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.
authors.affiliation: Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Amo
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kawanishi
authors.forename: Masataka
authors.initials: M
authors.lastname: Uchida
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujita
authors.forename: Eri
authors.initials: E
authors.lastname: Oyanagi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Utsumi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogino
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Kozo
authors.initials: K
authors.lastname: Utsumi
authors.forename: Junzo
authors.initials: J
authors.lastname: Sasaki
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005294:Ferrochelatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008027:Light; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D004791:Enzyme Inhibitors; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D005294:Ferrochelatase