TY - JOUR
T1 - Mechanism of cell death by 5-aminolevulinic acid-based photodynamic action and its enhancement by ferrochelatase inhibitors in human histiocytic lymphoma cell line U937
AU - Amo, Takashi
AU - Kawanishi, Noriaki
AU - Uchida, Masataka
AU - Fujita, Hirofumi
AU - Oyanagi, Eri
AU - Utsumi, Toshihiko
AU - Ogino, Tetsuya
AU - Inoue, Keiji
AU - Shuin, Taro
AU - Utsumi, Kozo
AU - Sasaki, Junzo
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - 5-aminolevulinic acid
KW - Apoptosis
KW - Ferrochelatase
KW - Photodynamic therapy
KW - Protoporphyrin IX
KW - U937 cell
UR - http://www.scopus.com/inward/record.url?scp=71949108405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71949108405&partnerID=8YFLogxK
U2 - 10.1002/cbf.1603
DO - 10.1002/cbf.1603
M3 - Article
C2 - 19735078
AN - SCOPUS:71949108405
VL - 27
SP - 503
EP - 515
JO - Cell Biochemistry and Function
JF - Cell Biochemistry and Function
SN - 0263-6484
IS - 8
ER -